scholarly journals Immunoprofiling Identifies Functional B and T Cell Subsets Induced by an Attenuated Whole Parasite Malaria Vaccine as Correlates of Sterile Immunity

Vaccines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 124
Author(s):  
Marie Mura ◽  
Pinyi Lu ◽  
Tanmaya Atre ◽  
Jessica S. Bolton ◽  
Elizabeth H. Duncan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Subsets ◽  
Computational Tools ◽  
Correlates Of Protection ◽  
Malaria Vaccines ◽  
Immune Correlates ◽  
Pathogen Challenge ◽  
Wide Range ◽  
B Cell Subsets

Immune correlates of protection remain elusive for most vaccines. An identified immune correlate would accelerate the down-selection of vaccine formulations by reducing the need for human pathogen challenge studies that are currently required to determine vaccine efficacy. Immunization via mosquito-delivered, radiation-attenuated P. falciparum sporozoites (IMRAS) is a well-established model for efficacious malaria vaccines, inducing greater than 90% sterile immunity. The current immunoprofiling study utilized samples from a clinical trial in which vaccine dosing was adjusted to achieve only 50% protection, thus enabling a comparison between protective and non-protective immune signatures. In-depth immunoprofiling was conducted by assessing a wide range of antigen-specific serological and cellular parameters and applying our newly developed computational tools, including machine learning. The computational component of the study pinpointed previously un-identified cellular T cell subsets (namely, TNFα-secreting CD8+CXCR3−CCR6− T cells, IFNγ-secreting CD8+CCR6+ T cells and TNFα/FNγ-secreting CD4+CXCR3−CCR6− T cells) and B cell subsets (i.e., CD19+CD24hiCD38hiCD69+ transitional B cells) as important factors predictive of protection (92% accuracy). Our study emphasizes the need for in-depth immunoprofiling and subsequent data integration with computational tools to identify immune correlates of protection. The described process of computational data analysis is applicable to other disease and vaccine models.

scholarly journals Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection

2020 ◽  
Author(s):  
Jessica B. Graham ◽  
Jessica L. Swarts ◽  
Sarah R. Leist ◽  
Alexandra Schäfer ◽  
Vineet D. Menachery ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Clinical Outcomes ◽  
Severe Disease ◽  
Collaborative Cross ◽  
Viral Control ◽  
Major Barrier ◽  
Mild Disease ◽  
Immune Correlates ◽  
Wide Range

AbstractThe COVID-19 pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans, from asymptomatic or mild disease to severe disease that can require mechanical ventilation. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit disease. This deficit is largely due to the lack of prospectively collected, pre-infection samples from indiviuals that go on to become infected with SARS-CoV-2. Here, we utilized data from a screen of genetically diverse mice from the Collaborative Cross (CC) infected with SARS-CoV to determine whether circulating baseline T cell signatures are associated with a lack of viral control and severe disease upon infection. SARS-CoV infection of CC mice results in a variety of viral load trajectories and disease outcomes. Further, early control of virus in the lung correlates with an increased abundance of activated CD4 and CD8 T cells and regulatory T cells prior to infections across strains. A basal propensity of T cells to express IFNg and IL17 over TNFa also correlated with early viral control. Overall, a dysregulated, pro-inflammatory signature of circulating T cells at baseline was associated with severe disease upon infection. While future studies of human samples prior to infection with SARS-CoV-2 are required, our studies in mice with SARS-CoV serve as proof of concept that circulating T cell signatures at baseline can predict clinical and virologic outcomes upon SARS-CoV infection. Identification of basal immune predictors in humans could allow for identification of individuals at highest risk of severe clinical and virologic outcomes upon infection, who may thus most benefit from available clinical interventions to restrict infection and disease.SummaryWe used a screen of genetically diverse mice from the Collaborative Cross infected with mouse-adapted SARS-CoV in combination with comprehensive pre-infection immunophenotyping to identify baseline circulating immune correlates of severe virologic and clinical outcomes upon SARS-CoV infection.

scholarly journals POS0003 RITUXIMAB THERAPY IN SYSTEMIC LUPUS ERYTHEMATOSUS – TRANSIENT EFFECTS ON AGE ASSOCIATED B-CELLS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 203.1-204
Author(s):  
F. Faustini ◽  
N. Sippl ◽  
R. Stålesen ◽  
K. Chemin ◽  
I. Gunnarsson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
T Cell Subsets ◽  
Cd4 Cells ◽  
Helper Cells ◽  
B Cell Subsets ◽  
Anti Cd20

Background:Immune system’s abnormalities in SLE involve several subsets of the B-cell compartment, including double negative B-cells (DN) and CD11c+CD21- B cells (also referred to as ABC-age associated B cells), which are expanded in the disease. ABC cells are also known to interact with T helper cells, T follicular and peripheral helper cells (1). Rituximab, a chimeric anti- CD20 antibody, depleting B cells, is commonly used off-label as treatment for SLE patients, especially in lupus nephritis. Little is known on the impact of B-cell depletion on such B-cell subsets and on B-T-cell interactions.Objectives:to investigate the effects of rituximab (RTX) on the frequencies of double negative B-cell subsets and CD11c+CD21- ABC cells and as well as T follicular helper (TFH, CXCR5+ PD-1+) and T peripheral helper (TPH, PD-1high) CD4+ T-cell subsets.Methods:15 SLE patients, starting RTX and followed longitudinally up to two years, were analyzed for lymphocyte subsets using multicolor flow cytometry. Cryopreserved PBMC were thawed and stained at the same time together with one buffy coat. Around 1 x 106 PBMC for each panel were labeled and further stained with fluorescent antibodies for B and T-cell markers. For the B-cell panel, PBMC were stained with anti-CD3, CD14, CD16, CD19, IgD, CD27, CD38, CD11c, CD21 and in some samples with anti-CXCR5 antibodies. For the T-cell panel, PBMC were labeled with anti-CD16, CD14, CD19 and CD3, CD4, CD8, PD-1, CCR7, CXCR5, CD45RA antibodies. All patients fulfilled the ACR 1982 classification criteria for SLE. Cellular changes were analyzed in the context of clinical information.Results:in the present cohort, the SLE patients were mainly female (86.6%) and of median age of 36.7 (29.8-49.4) with a disease duration of 6.1(1.6-11.8) years, and active disease with SLEDAI-2K at baseline 12.0 (8.0-16.0). The frequency of age-associated B cells (ABCs; CD27-IgD-CD11c+ CD21-) decreased by 13% (p=0.03) in the first two to four months after rituximab start, while globally the DN (IgD-CD27-) B cells transiently increased by around 3% (p=0.15) at the first follow-up. This increase could not be attributed to the DN1 (CXCR5+CD11c-) or DN2 (CXCR5-CD11c+) subsets but to the CD11c-CXCR5- DN (DN3) B cells (increase= 6.7%, p=0.03). In parallel, T effector cells (CCR7- CD45RA+) and TEMRA (CD45RA+ CCR7-) frequencies increased after first follow up in both CD4+ and CD8+ T cells. The frequency of TFH (CXCR5+ PD-1+) cells did not change after rituximab, however a decrease of PD-1high CD4+ cells was observed in most patients, although not significant, after 2-4 month of treatment. In most patients the frequency of PD-1high CD4+ cells either reduce or stay the same after RTX treatment (reduction= 0.53, p=0.28). After 11-15 months of RTX treatment the frequency of PD-1high CD4+ T cell reduces by a -0.5% in comparison to 2-4 months (p=0.039). The SLEDAI at baseline did not correlate with the frequency of PD-1high CD4+ T cells (r=0.03, p=0.9).Conclusion:the importance of T cell - B cell interactions in SLE pathogenesis was recently strengthened by the identification of the lymphocyte subsets TFH/TPH and ABCs respectively. Here, in the context of rituximab treated SLE, we could detect a reduction in the frequencies of both ABCs and PD-1high T cells after treatment with rituximab, while the DN3 and effector memory T cells frequencies increased. Our data suggests that anti-CD20 mediated B-cell depletion affects both B-cell and T-cell subsets frequencies, and that monitoring these specific cell subsets may be clinically relevant.References:[1]Bocharnikov AV, Keegan J, Wacleche VS, Cao Y, Fonseka CY, Wang G, et al. PD-1hiCXCR5- T peripheral helper cells promote B cell responses in lupus via MAF and IL-21. JCI insight. 2019;4(20)Disclosure of Interests:Francesca Faustini Speakers bureau: More than two years ago and not in relation to any aspect of the present research, Natalie Sippl: None declared, Ragnhild Stålesen: None declared, Karine Chemin: None declared, Iva Gunnarsson: None declared, Vivianne Malmström: None declared.

scholarly journals Phenotypic and Functional Profile of HIV-Inhibitory CD8 T Cells Elicited by Natural Infection and Heterologous Prime/Boost Vaccination

2010 ◽  
Vol 84 (10) ◽  
pp. 4998-5006 ◽  
Author(s):  
Stephanie A. Freel ◽  
Laurie Lamoreaux ◽  
Pratip K. Chattopadhyay ◽  
Kevin Saunders ◽  
David Zarkowsky ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiviral Activity ◽  
Recombinant Adenovirus ◽  
Natural Infection ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Multiparameter Flow Cytometry ◽  
Wide Range ◽  
Hiv 1

ABSTRACT Control of HIV-1 replication following nonsterilizing HIV-1 vaccination could be achieved by vaccine-elicited CD8+ T-cell-mediated antiviral activity. To date, neither the functional nor the phenotypic profiles of CD8+ T cells capable of this activity are clearly understood; consequently, little is known regarding the ability of vaccine strategies to elicit them. We used multiparameter flow cytometry and viable cell sorts from phenotypically defined CD8+ T-cell subsets in combination with a highly standardized virus inhibition assay to evaluate CD8+ T-cell-mediated inhibition of viral replication. Here we show that vaccination against HIV-1 Env and Gag-Pol by DNA priming followed by recombinant adenovirus type 5 (rAd5) boosting elicited CD8+ T-cell-mediated antiviral activity against several viruses with either lab-adapted or transmitted virus envelopes. As it did for chronically infected virus controllers, this activity correlated with HIV-1-specific CD107a or macrophage inflammatory protein 1β (MIP-1β) expression from HIV-1-specific T cells. Moreover, for vaccinees or virus controllers, purified memory CD8+ T cells from a wide range of differentiation stages were capable of significantly inhibiting virus replication. Our data define attributes of an antiviral CD8+ T-cell response that may be optimized in the search for an efficacious HIV-1 vaccine.

The Role of B and T Lymphocytes in Recurrent Acquired Thrombotic Thrombocytopenic Purpura.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3521-3521
Author(s):  
Mariagabriella Mariani ◽  
Andrea Cairo ◽  
Roberta Palla ◽  
Luca Andrea Lotta ◽  
Andrea Rovati ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cellular Immunity ◽  
T Cell Subsets ◽  
Surface Markers ◽  
Thrombocytopenic Purpura ◽  
B Cell Subsets

Abstract Abstract 3521 Poster Board III-458 Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disease characterized by thrombocytopenia, microangiopathic haemolytic anemia and widespread microvascular thrombosis, resulting in multiorgan ischemia. Acquired TTP, which accounts for approximately 95% of cases, can be either associated to anti ADAMTS13 autoantibodies or secondary to a number of associated conditions (tumors, organ transplantation, use of drugs, pregnancy). There are several key questions that remain unanswered, including the importance of cellular immunity in immunomediated TTP, and the search for laboratory markers that predict disease relapse, an event that occurs in 20% to 50% of patients who survive the acute initial episode. Since alterations of peripheral B and T cell subsets in patients with autoimmune diseases (i.e. rheumatoid arthritis and systemic lupus erythematous) are well established, the aim of this study was to analyze the role of B and T cells in acquired TTP and during its recurrence. Methods 36 healthy controls and 36 consecutive patients affected by acquired TTP during remission (defined as the maintenance of normalization of clinical and laboratory data for at least 30 days after the last plasma therapy following the resolution of the last acute episode) were characterized by flow cytometry for the quantification of: - different peripheral B cell subsets, using labeled surface markers anti-CD19-PerCP, anti-IgD-PE, anti-IgM-FITC, anti-CD27-APC, anti-CD38-FITC; - different peripheral T cell subsets, using labeled surface markers anti-CD3-FITC, anti-CD4-PE, anti-CD8-APC, anti-CD25-FITC. For Treg cell quantification (only 17 patients were analyzed), anti-CD3-PerCP, anti-CD4-FITC, anti-CD25-PE and the intracellular marker FoxP3 were used. Patients were classified in two subgroups: those who developed at least two episodes of TTP (n=19, with recurrence) and those who experienced a single episode only and no relapse during at least one year of retrospective observational time (n=17). ADAMTS13 activity was measured by residual collagen binding assay (Gerritsen et al, Thromb Haemost 1999). The presence of anti-ADAMTS13 IgG was evaluated by Western blotting and ELISA assays, using recombinant ADAMTS13 protein as antigen and patients' plasma as a source of antibody. The presence of anti-ADAMTS13 IgA, IgM, IgG subclasses (IgG1, 2, 3, 4) were evaluated by ELISA assays. For continuous variables, differences between controls and patients and between patients with or without recurrence were evaluated by the t-test; for discrete variables, by the chi square test. P values smaller than 0.05 were considered statistically significant. Analyses were performed using the SPSS package version 17.0. Results 1) TTP patients had an increased number of CD19+ B cells (mean ± SD 13% ± 5) compared with the control group (10% ± 3, p=0.001). No difference was observed in T cells subsets. 2) The results of the characterization of the two groups of patients (with and without recurrence) are reported in the table. Patients with and without recurrence did not differ either in the amount of Treg FoxP3 or in the presence of IgA, IgM and IgG subclasses. Discussion The increased B cell numbers in acquired TTP indicates an enhanced activation of cellular immunity. Analysis of B cell subsets, particularly of memory B cells, and of T cells CD24+CD25+ during remission might provide information on the likelihood of recurrence in TTP. In conclusion, in recurrent TTP patients the higher amount of B cells might result in persistent autoantibodies production whilst the decreased level of T cells CD4+CD25+ may lead to a decreased inhibition of autoreactive T cells. These findings may explain the higher level of recurrence in these patients. Disclosures: Peyvandi: Archemix Corporation: Consultancy.

scholarly journals BpOmpW Antigen Stimulates the Necessary Immune Correlates of Protection Against Melioidosis

2021 ◽  
Author(s):  
Julen Tomas-Cortazar ◽  
Siobhan McClean
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Nkt Cells ◽  
Control Group ◽  
Insulin Resistant ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Hla Dq

Melioidosis is a fatal disease caused by Burkholderia pseudomallei Gram-negative bacteria. It is the causative of 89,000 deaths per year in endemic areas of Southeast Asia and Northern Australia. Diabetes mellitus is the most risk factor, increasing 12-fold the susceptibility for severe disease. IFN-y responses from CD4 and CD8 T cells, but also from NK and NKT cells are necessary to eliminate the pathogen. Elucidating the immune correlates of protection of our previously described protective BpOmpW vaccine is an essential step of any vaccine before clinical trials. Thus, we immunized non-insulin resistant C57BL/6j mice and an insulin resistant C57BL/6j mouse model of Type 2 Diabetes (T2D) with BpOmpW using Sigma Adjuvant System (SAS) (treatment) or SAS only (control). Two weeks later bloods and spleens were collected and serological analysis & in vitro exposure of splenocytes to the antigen for 60 hours were performed in both controls and treatment groups to finally analyze the stained splenocytes by flow cytometry. BpOmpW induced strong antibody response, stimulated effector CD4+ and CD8+ T cells and CD4+ CD25+ Foxp3+regulatory T cells and produced higher IFN-y; responses in CD4+, CD8+, NK and NKT cells relative to the control group in non-insulin resistant mice. T cell responses of insulin resistant mice to BpOmpW were comparable to those in non-insulin resistant mice. In addition, as a precursor to its evaluation in human studies, humanised HLA-DR and HLA-DQ transgenic mice elicited IFN-y; recall responses in an ELISPoT-based study and PBMCs from donors that were in contact to BpOmpW for seven days experienced T cell proliferation. Finally, plasma from melioidosis survivors with diabetes recognized our BpOmpW vaccine antigen. Overall, these range of approaches used strongly indicate that BpOmpW elicits the required immune correlates of protection to combat melioidosis and bring the vaccine closer to clinical trials.

scholarly journals Age-Specific Imbalance of Circulating Tfh Cell Subsets and Its Association With Gout-Targeted Kidney Impairment

2021 ◽  
Vol 11 ◽  
Author(s):  
Yefei Huang ◽  
Xinyu Wu ◽  
Lian Gui ◽  
Yutong Jiang ◽  
Liudan Tu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Renal Dysfunction ◽  
Clinical Features ◽  
T Cell Subsets ◽  
Th2 Cells ◽  
Color Flow ◽  
B Cell Subsets

ObjectiveGout is a chronic disease characterized by the deposition of monosodium urate (MSU) crystals in tissue. Study with a focus on adaptive immune response remains to be understood although innate immune response has been reported extensively in gout etiology. Our study attempted to investigate the association of gout-related immune cell imbalance with clinical features and comorbidity with renal impairment and the implicated pathogenesis via the assessment of T and B cell subsets in different activity phases or with immune effects combined with the analyses of clinical parameters.MethodsFifty-eight gout patients and 56 age- and sex-matched healthy individuals were enrolled. To learn the roles of circulating T cells, a lymphocyte profile incorporating 32 T cell subsets was tested from isolated freshly peripheral blood monocyte cells (PBMCs) with multiple-color flow cytometry. Furthermore, the collected clinical features of participants were used to analyze the characteristics of these differential cell subsets. Stratified on the basis of the level of creatinine (Cr, enzymatic method), all patients were categorized into Crlow (Cr ≤ 116 μmol/L) and Crhi (Cr > 116 μmol/L) groups to exploit whether these gout-associated T cell subsets were functional in gout-targeted kidney dysfunction. The differentiation of B cells was investigated in gout patients.ResultsOur results show that CD 4+ T cells, Th2 cells, and Tc2 cells were upregulated, whereas Tc17 cells were downregulated. Tfh cells skewed toward the polarization of Tfh2 cells. Specifically, Tfh2 cells increased, but Tfh1 cells decreased, accompanied with aging for gout patients, suggesting that age might trigger the skewing of Tfh1/Tfh2 cell subsets to influence gout development. Moreover, Tfh2 cells were connected to renal dysfunction as well. No alterations of B cell subsets were observed in patients when compared to controls.ConclusionsOur data demonstrate age-specific dysfunctions of Tfh1/2 cells in gout occurrence, and Tfh2 cell upregulation is associated with gout-targeted renal dysfunction. However, Tfh2 cells may function in auto-inflammatory gout independent of helping B differentiation, and an in-depth study remains to be conducted.

scholarly journals Traditional Thai Massage Promoted Immunity in the Elderly via Attenuation of Senescent CD4+ T Cell Subsets: A Randomized Crossover Study

2021 ◽  
Vol 18 (6) ◽  
pp. 3210
Author(s):  
Kanda Sornkayasit ◽  
Amonrat Jumnainsong ◽  
Wisitsak Phoksawat ◽  
Wichai Eungpinichpong ◽  
Chanvit Leelayuwat
Keyword(s):  
T Cells ◽  
T Cell ◽  
Crossover Study ◽  
Intracellular Cytokine Staining ◽  
The Elderly ◽  
Complementary Therapy ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
T Subsets ◽  
Randomized Crossover Study

The beneficial physiological effects of traditional Thai massage (TTM) have been previously documented. However, its effect on immune status, particularly in the elderly, has not been explored. This study aimed to investigate the effects of multiple rounds of TTM on senescent CD4+ T cell subsets in the elderly. The study recruited 12 volunteers (61–75 years), with senescent CD4+ T cell subsets, who received six weekly 1-h TTM sessions or rest, using a randomized controlled crossover study with a 30-day washout period. Flow cytometry analysis of surface markers and intracellular cytokine staining was performed. TTM could attenuate the senescent CD4+ T cell subsets, especially in CD4+28null NKG2D+ T cells (n = 12; p < 0.001). The participants were allocated into two groups (low < 2.75% or high ≥ 2.75%) depending on the number of CD4+28null NKG2D+ T cells. After receiving TTM over 6 sessions, the cell population of the high group had significantly decreased (p < 0.001), but the low group had no significant changes. In conclusion, multiple rounds of TTM may promote immunity through the attenuation of aberrant CD4+ T subsets. TTM may be provided as a complementary therapy to improve the immune system in elderly populations.

scholarly journals 413 GEN-009, a personalized neoantigen vaccine, elicits robust immune responses in individuals with advanced or metastatic solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A438-A438
Author(s):  
Mara Shainheit ◽  
Devin Champagne ◽  
Gabriella Santone ◽  
Syukri Shukor ◽  
Ece Bicak ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Solid Tumors ◽  
Ex Vivo ◽  
T Cell Responses ◽  
Checkpoint Blockade ◽  
T Cell Subsets ◽  
Cell Responses

BackgroundATLASTM is a cell-based bioassay that utilizes a cancer patient‘s own monocyte-derived dendritic cells and CD4+ and CD8+ T cells to screen their mutanome and identify neoantigens that elicit robust anti-tumor T cell responses, as well as, deleterious InhibigensTM.1 GEN-009, a personalized vaccine comprised of 4–20 ATLAS-identified neoantigens combined with Hiltonol®, harnesses the power of neoantigen-specific T cells to treat individuals with solid tumors. The safety and efficacy of GEN-009 is being assessed in a phase 1/2a clinical trial (NCT03633110).MethodsA cohort of 15 adults with solid tumors were enrolled in the study. During the screening period, patients received standard of care PD-1-based immunotherapies appropriate for their tumor type. Subsequently, patients were immunized with GEN-009 with additional doses administered at 3, 6, 12, and 24 weeks. Peripheral blood mononuclear cells (PBMCs) were collected at baseline, pre-vaccination (D1), as well as 29, 50, 92, and 176 days post first dose. Vaccine-induced immunogenicity and persistence were assessed by quantifying neoantigen-specific T cell responses in ex vivo and in vitro stimulation dual-analyte fluorospot assays. Polyfunctionality of neoantigen-specific T cells was evaluated by intracellular cytokine staining. Additionally, potential correlations between the ATLAS-identified profile and vaccine-induced immunogenicity were assessed.ResultsGEN-009 augmented T cell responses in 100% of evaluated patients, attributable to vaccine and not checkpoint blockade. Furthermore, neoantigen-induced secretion of IFNγ and/or TNFα by PBMCs, CD4+, and CD8+ T cells was observed in all patients. Responses were primarily from polyfunctional TEM cells and detectable in both CD4+ and CD8+ T cell subsets. Some patients had evidence of epitope spreading. Unique response patterns were observed for each patient with no apparent relationship between tumor types and time to emergence, magnitude or persistence of response. Ex vivo vaccine-induced immune responses were observed as early as 1 month, and in some cases, persisted for 176 days. Clinical efficacy possibly attributable to GEN-009 was observed in several patients, but no correlation has yet been identified with neoantigen number or magnitude of immune response.ConclusionsATLAS empirically identifies stimulatory neoantigens using the patient‘s own immune cells. GEN-009, which is comprised of personalized, ATLAS-identified neoantigens, elicits early, long-lasting and polyfunctional neoantigen-specific CD4+ and CD8+ T cell responses in individuals with advanced cancer. Several patients achieved clinical responses that were possibly attributable to vaccine; efforts are underway to explore T cell correlates of protection. These data support that GEN-009, in combination with checkpoint blockade, represents a unique approach to treat solid tumors.AcknowledgementsWe are grateful to the patients and their families who consented to participate in the GEN-009-101 clinical trial.Trial RegistrationNCT03633110Ethics ApprovalThis study was approved by Western Institutional Review Board, approval number 1-1078861-1. All subjects contributing samples provided signed individual informed consent.ReferenceDeVault V, Starobinets H, Adhikari S, Singh S, Rinaldi S, Classon B, Flechtner J, Lam H. Inhibigens, personal neoantigens that drive suppressive T cell responses, abrogate protection of therapeutic anti-tumor vaccines. J. Immunol 2020; 204(1 Supplement):91.15.

scholarly journals The role of unconventional T cells in COVID-19

2021 ◽  
Author(s):  
Kristen Orumaa ◽  
Margaret R. Dunne
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Treatment Strategies ◽  
Γδ T Cells ◽  
Protective Role ◽  
T Cell Subsets ◽  
Viral Immunity ◽  
Mait Cells

AbstractCOVID-19 is a respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first documented in late 2019, but within months, a worldwide pandemic was declared due to the easily transmissible nature of the virus. Research to date on the immune response to SARS-CoV-2 has focused largely on conventional B and T lymphocytes. This review examines the emerging role of unconventional T cell subsets, including γδ T cells, invariant natural killer T (iNKT) cells and mucosal associated invariant T (MAIT) cells in human SARS-CoV-2 infection.Some of these T cell subsets have been shown to play protective roles in anti-viral immunity by suppressing viral replication and opsonising virions of SARS-CoV. Here, we explore whether unconventional T cells play a protective role in SARS-CoV-2 infection as well. Unconventional T cells are already under investigation as cell-based immunotherapies for cancer. We discuss the potential use of these cells as therapeutic agents in the COVID-19 setting. Due to the rapidly evolving situation presented by COVID-19, there is an urgent need to understand the pathogenesis of this disease and the mechanisms underlying its immune response. Through this, we may be able to better help those with severe cases and lower the mortality rate by devising more effective vaccines and novel treatment strategies.

scholarly journals Single-cell analysis reveals cell communication triggered by macrophages associated with the reduction and exhaustion of CD8+ T cells in COVID-19

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lei He ◽  
Quan Zhang ◽  
Yue Zhang ◽  
Yixian Fan ◽  
Fahu Yuan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Cell Communication ◽  
Cell Types ◽  
Trial Registration ◽  
T Cell Subsets ◽  
Disease Group ◽  
Communication Analysis ◽  
Receptor Interactions

Abstract Background The coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has become an ongoing pandemic. Understanding the respiratory immune microenvironment which is composed of multiple cell types, together with cell communication based on ligand–receptor interactions is important for developing vaccines, probing COVID-19 pathogenesis, and improving pandemic control measures. Methods A total of 102 consecutive hospitalized patients with confirmed COVID-19 were enrolled in this study. Clinical information, routine laboratory tests, and flow cytometry analysis data with different conditions were collected and assessed for predictive value in COVID-19 patients. Next, we analyzed public single-cell RNA-sequencing (scRNA-seq) data from bronchoalveolar lavage fluid, which offers the closest available view of immune cell heterogeneity as encountered in patients with varying severity of COVID-19. A weighting algorithm was used to calculate ligand–receptor interactions, revealing the communication potentially associated with outcomes across cell types. Finally, serum cytokines including IL6, IL1β, IL10, CXCL10, TNFα, GALECTIN-1, and IGF1 derived from patients were measured. Results Of the 102 COVID-19 patients, 42 cases (41.2%) were categorized as severe. Multivariate logistic regression analysis demonstrated that AST, D-dimer, BUN, and WBC were considered as independent risk factors for the severity of COVID-19. T cell numbers including total T cells, CD4+ and CD8+ T cells in the severe disease group were significantly lower than those in the moderate disease group. The risk model containing the above mentioned inflammatory damage parameters, and the counts of T cells, with AUROCs ranged from 0.78 to 0.87. To investigate the molecular mechanism at the cellular level, we analyzed the published scRNA-seq data and found that macrophages displayed specific functional diversity after SARS-Cov-2 infection, and the metabolic pathway activities in the identified macrophage subtypes were influenced by hypoxia status. Importantly, we described ligand–receptor interactions that are related to COVID-19 serverity involving macrophages and T cell subsets by communication analysis. Conclusions Our study showed that macrophages driving ligand–receptor crosstalk contributed to the reduction and exhaustion of CD8+ T cells. The identified crucial cytokine panel, including IL6, IL1β, IL10, CXCL10, IGF1, and GALECTIN-1, may offer the selective targets to improve the efficacy of COVID-19 therapy. Trial registration: This is a retrospective observational study without a trial registration number.

Sign in / Sign up

Export Citation Format

Share Document