t cell immune responses
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Author(s):  
Pablo Barreiro ◽  
Juan Carlos Sanz ◽  
Jesús San Román ◽  
Marta Pérez-Abeledo ◽  
Mar Carretero ◽  
...  

Background: Assessment of T-cell responses to SARS-CoV-2 antigens may be of value to determine long-lasting protection to breakthrough infections or reinfections. Interferon-gamma release assay is a validated method to test cellular immunity in mycobacterial infections and has been proposed for patients with SARS-CoV-2 infection or vaccination. Methods: Quantitative IgG to spike and qualitative IgG to nucleocapsid antigens were determined by chemiluminescence microparticle immunoassay using the Architect® platform (Abbott®), and interferon-gamma release assay against two Qiagen® proprietary mixes of SARS-CoV-2 spike protein (antigen-1 and antigen-2) were performed for a selected group of subjects. Results: A total of 121 subjects in a cloistered institution after a COVID-19 outbreak were studied. IgG-spike levels and interferon-gamma concentration were highest among subjects after two doses of vaccine, followed by patients with a longer history of past COVID-19 and no vaccination. Best cut-off for interferon-gamma assay was 25 IU/μL for all subgroups of individuals and the two sets of SARS-CoV-2 antigens studied. Conclusions: Testing T-cell response may be of clinical utility to determine immunity after exposure to SARS-CoV-2 antigens, with the interferon-gamma concentration of 25 IU/μL as the best cut-off either after infection or vaccination.


2021 ◽  
pp. 2100082
Author(s):  
Silvana Geisshüsler ◽  
Philipp Schineis ◽  
Lara Langer ◽  
Ying Wäckerle-Men ◽  
Jean-Christophe Leroux ◽  
...  

Blood ◽  
2021 ◽  
Author(s):  
Adèle de Masson ◽  
Delphine Darbord ◽  
Gabor Dobos ◽  
Marie Boisson ◽  
Marie Roelens ◽  
...  

Cutaneous T-cell lymphoma (CTCL) is a malignancy of skin-homing T-cells. Long-term remissions are rare in CTCL, and the pathophysiology of long-lasting disease control is unknown. Mogamulizumab is a defucosylated anti-human CCR4 antibody that depletes CCR4-expressing CTCL tumor cells and peripheral blood memory regulatory T cells. Prolonged remissions and immune side effects have been observed in mogamulizumab-treated CTCL patients. We report that mogamulizumab induced skin rashes in 32% of 44 CTCL patients. These rashes were associated with long-term CTCL remission, even in the absence of specific CTCL treatment. CTCL patients with mogamulizumab-induced rash had significantly higher overall survival (hazard ratio, 0.16 (0.04-0.73, p=0.01)). Histopathology and immunohistochemistry of the rashes revealed granulomatous and lichenoid patterns with CD163 macrophagic and CD8 T-cell infiltrates. Depletion of skin CTCL cells was confirmed by high-throughput sequencing analysis of TCRβ genes and in blood by flow cytometry. New reactive T-cell clones were recruited in skin. Gene expression analysis showed overexpression of CXCL9 and CXCL11, two chemokines involved in CXCR3-expressing T-cell homing to skin. Single-cell RNA sequencing analysis in skin of CTCL patients confirmed that CXCL9 and CXCL11 were primarily macrophage-derived and that skin T-cells expressed CXCR3. Finally, patients with rashes had a significantly higher proportion of exhausted reactive blood T-cells expressing TIGIT and PD1 at baseline compared to patients without rash, which decreased under mogamulizumab treatment, consistent with an activation of the antitumor immunity. Together, these data suggest that mogamulizumab may induce long-term immune control in CTCL patients by activation of the macrophagic and T-cell immune responses.


2021 ◽  
Vol 2 ◽  
Author(s):  
Jun Jin ◽  
Huimin Zhang ◽  
Cornelia M. Weyand ◽  
Jorg J. Goronzy

Lysosomes were initially recognized as degradation centers that regulate digestion and recycling of cellular waste. More recent studies document that the lysosome is an important signaling hub that regulates cell metabolism. Our knowledge of the role of lysosomes in immunity is mostly derived from innate immune cells, especially lysosomal degradation-specialized cells such as macrophages and dendritic cells. Their function in adaptive immunity is less understood. However, with the recent emphasis on metabolic regulation of T cell differentiation, lysosomes are entering center stage in T cell immunology. In this review, we will focus on the role of lysosomes in adaptive immunity and discuss recent findings on lysosomal regulation of T cell immune responses and lysosomal dysfunction in T cell aging.


2021 ◽  
Author(s):  
Chien-Sheng Wu ◽  
Hsiu-Jung Liao ◽  
I-Tsu Chyuan ◽  
Szu-Chieh Wang ◽  
Hua-Yi Lee ◽  
...  

Abstract Recent emerging evidences indicate that dysfunction of metabolic remodeling underlies aberrant T cell immune responses in systemic lupus erythematosus (SLE). However, how these aberrant immune activation and metabolic dysfunction interact in lupus patients are not fully understood. This study was undertaken to investigate the expression of HIF-1α, a regulator of metabolic reprogramming, in T cells from SLE. Our results demonstrated that HIF-1α expression is increased in CD4 T cells from SLE patients both in intracellular staining and quantitative real-time PCR analysis. In addition, there is enhanced HIF-1α expression in Th17-skewing murine T cells, and lentivirus-mediated HIF-1α overexpression promotes Th17 differentiation. Moreover, HIF-1α gene expression is positively correlated with the expression of glycolysis- and IL-17-associated genes in SLE patients. These results indicate that HIF-1α expression is increased in T cells from SLE patients, and is associated with enhanced Th17 pathway, implicating HIF-1α contributes to the activation of Th17 cells in SLE, and represents a potential novel therapeutic target.


Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1392
Author(s):  
Peter Lawrence Smith ◽  
Katarzyna Piadel ◽  
Angus George Dalgleish

Cancer vaccination and immunotherapy revolutionised the treatment of cancer, a result of decades of research into the immune system in health and disease. However, despite recent breakthroughs in treating otherwise terminal cancer, only a minority of patients respond to cancer immunotherapy and some cancers are largely refractive to immunotherapy treatment. This is due to numerous issues intrinsic to the tumour, its microenvironment, or the immune system. CD4+ and CD8+ αβ T-cells emerged as the primary effector cells of the anti-tumour immune response but their function in cancer patients is often compromised. This review details the mechanisms by which T-cell responses are hindered in the setting of cancer and refractive to immunotherapy, and details many of the approaches under investigation to direct T-cell function and improve the efficacy of cancer vaccination and immunotherapy.


Author(s):  
Lidewij W Rümke ◽  
Femke C Groenveld ◽  
Yvonne M G van Os ◽  
Patrique Praest ◽  
Anniek A N Tanja ◽  
...  

Abstract SARS-CoV-2 infection after COVID-19 vaccination raises concerns about the emergence of vaccine escape variants. Here we characterize 14 breakthrough infections among 5860 fully vaccinated Dutch healthcare workers ≥14 days post final dose of vaccination with either BNT162b2, mRNA-1273 or Ad26.COV2.S. These breakthrough infections presented with regular B.1.1.7 (Alpha) and B.1.617.2 (Delta) variants and high viral loads, despite normal vaccine induced B- and T-cell immune responses detected by live virus neutralization assays and ELISpot. High-risk exposure settings, such as in households, indicate a potential risk of viral transmission despite full vaccination.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1757-1757
Author(s):  
Kalpana Parvathaneni ◽  
Kyabeth Toress-Rodriguez ◽  
Wenzhao Meng ◽  
James Knox ◽  
Xiaoming Xu ◽  
...  

Abstract Abstract Background: The two FDA approved mRNA-based SARS-CoV2 vaccines have shown >90% efficacy at preventing COVID and eliciting protective immunity in nearly all healthy individuals. However, the extent of vaccine induced antibody and T cell immunity in immunocompromised patients is not well known. Our study objective is to determine if patients with hematologic malignancies treated with B-cell targeting chimeric antigen receptor (CAR) T cell therapies can mount antibody and T cell immune responses to SARS-CoV2 vaccines. A prospective single-center study to evaluate the SARS-CoV2 immune responses in immunocompromised individuals (COVAX Study) was initiated at University of Pennsylvania following the IRB guidelines. The study enrolled 8 healthy adults,12 patients are in remission after treatment (average of 40.6 months) with CART cells targeting either CD19 or CD19+CD22 and received both doses of SARS-CoV2 vaccine. Methods and Results: Serology to SARS-CoV2 spike-receptor binding domain (RBD) IgG, RBD-IgA, RBD-IgM and spike-specific T cell responses were measured prior to vaccination and serially up to 28 days after booster vaccination. RBD-IgG and RBD-IgA were detected in 8/8 and 7/8 healthy subjects compared to 5/12 and 2/12 CART patients, respectively (Figure A). In the CART cohort, several patients who demonstrated an induction of RBD-IgG (57.2/uL +/- 20.2) compared to those who were RBD-IgG-negative (9/uL +/- 10.1, ANOVA with multiple comparisons test p=0.017) have higher level of circulating B cells. No association was found with time since CART infusion, age, disease type, or vaccine manufacturer. All 8 healthy subjects demonstrated induction of SARS-Cov2 spike-specific CD4 + T cell immunity compared to 7 out of 11 CART patients (Figure B). RBD-IgG responses were not correlated with CD4 + T cell activation (Pearson correlation, R=0.21, p=0.53). Indeed, 3 CART patients demonstrated robust CD4 + T cell activation despite absence of antibody induction. Overall, 8/12 CART patients demonstrated induction of either or both humoral and T cell immune responses. Conclusions: We show that immune responses to SARS-CoV2 mRNA vaccines are induced in majority of patients who have been treated with CART therapies targeting B-cell lineage antigens. Induction of vaccine-specific antibody was strongly associated with the level of circulating B cells. However, in CART cohort patients despite severe humoral immune deficiency, strong CD4 + T cell responses were observed suggestive of a sufficient protective immunity. Figure 1 Figure 1. Disclosures Frey: Novartis: Research Funding; Sana Biotechnology: Consultancy; Kite Pharma: Consultancy; Syndax Pharmaceuticals: Consultancy. Garfall: Amgen: Honoraria; CRISPR Therapeutics: Research Funding; GlaxoSmithKline: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Research Funding; Tmunity: Research Funding. Porter: American Society for Transplantation and Cellular Therapy: Honoraria; Genentech: Current equity holder in publicly-traded company, Ended employment in the past 24 months; ASH: Membership on an entity's Board of Directors or advisory committees; DeCart: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Tmunity: Patents & Royalties; Wiley and Sons Publishing: Honoraria. June: AC Immune, DeCART, BluesphereBio, Carisma, Cellares, Celldex, Cabaletta, Poseida, Verismo, Ziopharm: Consultancy; Tmunity, DeCART, BluesphereBio, Carisma, Cellares, Celldex, Cabaletta, Poseida, Verismo, Ziopharm: Current equity holder in publicly-traded company; Novartis: Patents & Royalties.


EBioMedicine ◽  
2021 ◽  
Vol 73 ◽  
pp. 103636
Author(s):  
Sachin P. Gadani ◽  
Maria Reyes-Mantilla ◽  
Larissa Jank ◽  
Samantha Harris ◽  
Morgan Douglas ◽  
...  

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