scholarly journals Detection of Antigen-Specific T Cells Using In Situ MHC Tetramer Staining

2019 ◽  
Vol 20 (20) ◽  
pp. 5165 ◽  
Author(s):  
Hadia M. Abdelaal ◽  
Emily K. Cartwright ◽  
Pamela J. Skinner
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Bacterial Infections ◽  
Dimensional Space ◽  
Cell Immune Response ◽  
3 Dimensional ◽  
History Of ◽  
Specific Tissue ◽  
Cellular Immune

The development of in situ major histocompatibility complex (MHC) tetramer (IST) staining to detect antigen (Ag)-specific T cells in tissues has radically revolutionized our knowledge of the local cellular immune response to viral and bacterial infections, cancers, and autoimmunity. IST combined with immunohistochemistry (IHC) enables determination of the location, abundance, and phenotype of T cells, as well as the characterization of Ag-specific T cells in a 3-dimensional space with respect to neighboring cells and specific tissue locations. In this review, we discuss the history of the development of IST combined with IHC. We describe various methods used for IST staining, including direct and indirect IST and IST performed on fresh, lightly fixed, frozen, and fresh then frozen tissue. We also describe current applications for IST in viral and bacterial infections, cancer, and autoimmunity. IST combined with IHC provides a valuable tool for studying and tracking the Ag-specific T cell immune response in tissues.

scholarly journals Immunosequencing and epitope mapping reveal substantial preservation of the T cell immune response to Omicron generated by SARS-CoV-2 vaccines

2021 ◽  
Author(s):  
Damon H. May ◽  
Benjamin E. R. Rubin ◽  
Sudeb C. Dalai ◽  
Krishna Patel ◽  
Shahin Shafiani ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cellular Immune Response ◽  
Epitope Mapping ◽  
Protective Efficacy ◽  
T Cell Response ◽  
Cell Immune Response ◽  
Cell Immunity ◽  
Cellular Immune

The Omicron SARS-CoV-2 variant contains 34 mutations in the spike gene likely impacting protective efficacy from vaccines. We evaluated the potential impact of these mutations on the cellular immune response. Combining epitope mapping to SARS-CoV-2 vaccines that we have determined from past experiments along with T cell receptor (TCR) repertoire sequencing from thousands of vaccinated or naturally infected individuals, we estimate the abrogation of the cellular immune response in Omicron. Although 20% of CD4+ T cell epitopes are potentially affected, the loss of immunity mediated by CD4+ T cells is estimated to be slightly above 30% as some of the affected epitopes are relatively more immunogenic. For CD8+ T cells, we estimate a loss of approximately 20%. These reductions in T cell immunity are substantially larger than observed in other widely distributed variants. Combined with the expected substantial loss of neutralization from antibodies, the overall protection provided by SARS-CoV-2 vaccines could be impacted adversely. From analysis of prior variants, the efficacy of vaccines against symptomatic infection has been largely maintained and is strongly correlated with the T cell response but not as strongly with the neutralizing antibody response. We expect the remaining 70% to 80% of on-target T cells induced by SARS-CoV-2 vaccination to reduce morbidity and mortality from infection with Omicron.

scholarly journals Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexandra J. Spencer ◽  
Paul F. McKay ◽  
Sandra Belij-Rammerstorfer ◽  
Marta Ulaszewska ◽  
Cameron D. Bissett ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
T Cells ◽  
Immune Responses ◽  
Viral Vectors ◽  
Cytotoxic T Cells ◽  
Antibody Responses ◽  
Limited Data ◽  
Vectored Vaccine ◽  
Cellular Immune

AbstractSeveral vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two-dose heterologous vaccination regimens than single-dose regimens. Neutralising titres after heterologous prime-boost were at least comparable or higher than the titres measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells, which is superior to the response induced in homologous vaccination regimens in mice. These results underpin the need for clinical trials to investigate the immunogenicity of heterologous regimens with alternate vaccine technologies.

scholarly journals Importance of cellular immunity link for efficiency of replacement therapy in common variable immune deficiency

2020 ◽  
Vol 22 (4) ◽  
pp. 799-804
Author(s):  
L. P. Sizyakina ◽  
I. I. Andreeva ◽  
D. I. Danilova
Keyword(s):  
Immune Response ◽  
Replacement Therapy ◽  
Cellular Immunity ◽  
Bacterial Infections ◽  
Immune Cell ◽  
Respiratory Infections ◽  
Combined Treatment ◽  
Ivig Therapy ◽  
Continuous Treatment ◽  
Cellular Immune

Lifetime use of IgG replacement therapy  is the standard of CVID treatment. However, full control over stabilization of chronic infection loci is not always achieved, even if this therapy  is continuously applied. The purpose  of this study was to carry out comparative analysis of changes  in cellular  component of adaptive and  innate immune response, depending on effectiveness of replacement therapy  of patients with infectious CVID  phenotype. The  observation group  consisted of 15 patients with  CVID  who  were  diagnosed since early childhood in 100% of cases. They had prolonged respiratory infections followed by the development of complications requiring continuous treatment with antibiotics.After  reaching mean  age of 15 years  old,  the  intensity of infection-associated antibody deficiency was 6-8  times  per year. After verification of the  diagnosis, the  patients received  replacement therapy, first at the saturation dose,  and,  after stabilization of IgG  at the level of 7-8 g/l,  at the monthly maintenance dose. The clinical  course  of the disease was traced  during  a full year of replacement therapy, and the cellular  immunity indices  were evaluated. In all patients, after a year of therapy  corresponding to clinical  guidelines, there  was an improvement in quality  of life indices, decreased rates of recurrent bacterial infections. At the same time, 40% of them continued to suffer, on average, 5.4±1.1 times a year and required long-term courses of antibiotic therapy. Evaluation of immune status did not reveal statistically significant  differences in IgG plasma saturation between the groups of patients with different treatment efficiency: 8.7 (8-9) g/l and 9.1 (8.5-10.5) g/l, at p = 0.5. The  differences related  to immune cell factors  in cases of smaller  effect of IVIG  therapy  are manifested in higher  relative  numbers of T effectors  containing lytic Granzyme B granules  and CD14+CD284+  monocytes, accompanied by lower spontaneous active  oxygen forms produced by neutrophils, lesser contents of CD16+ natural killers in peripheral blood.The obtained data illustrate the value of monitoring, not only serum  IgG  level, but also the parameters of the  cellular  immune response. Such  analysis  may be essential  as a prognostic criterion for efficacy  of IVIG therapy. Reduced levels of some parameters of innate immunity cells serves a basis to formulate the concept of combined treatment and usage of tools that alter functions of immunocompetent cells.

scholarly journals Divergent Impact of Glucose Availability on Human Virus-Specific and Generically Activated CD8 T Cells

Metabolites ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 461
Author(s):  
Jenifer Sanchez ◽  
Ian Jackson ◽  
Katie R. Flaherty ◽  
Tamara Muliaditan ◽  
Anna Schurich
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Function ◽  
Cd8 T Cell ◽  
Cell Immune Response ◽  
Complex Nature ◽  
Human Virus ◽  
Glucose Availability

Upon activation T cells engage glucose metabolism to fuel the costly effector functions needed for a robust immune response. Consequently, the availability of glucose can impact on T cell function. The glucose concentrations used in conventional culture media and common metabolic assays are often artificially high, representing hyperglycaemic levels rarely present in vivo. We show here that reducing glucose concentration to physiological levels in culture differentially impacted on virus-specific compared to generically activated human CD8 T cell responses. In virus-specific T cells, limiting glucose availability significantly reduced the frequency of effector-cytokine producing T cells, but promoted the upregulation of CD69 and CD103 associated with an increased capacity for tissue retention. In contrast the functionality of generically activated T cells was largely unaffected and these showed reduced differentiation towards a residency phenotype. Furthermore, T cells being cultured at physiological glucose concentrations were more susceptible to viral infection. This setting resulted in significantly improved lentiviral transduction rates of primary cells. Our data suggest that CD8 T cells are exquisitely adapted to their niche and provide a reminder of the need to better mimic physiological conditions to study the complex nature of the human CD8 T cell immune response.

In situ study of cellular immune response in human cutaneous lesions caused by Leishmania (Viannia) panamensis in Panama

2020 ◽  
Author(s):  
Kadir Gonzalez ◽  
José Eduardo Calzada ◽  
Thaise Yumie Tomokane ◽  
Carmen Maria Sandoval Pacheco ◽  
Gabriela Venicia Araujo Flores ◽  
...  
Keyword(s):  
Immune Response ◽  
Cellular Immune Response ◽  
Cutaneous Lesions ◽  
In Situ Study ◽  
Cellular Immune

scholarly journals Comparative Evaluation of T-Cell Immune Response to BTV Infection in Sheep Vaccinated with Pentavalent BTV Vaccine When Compared to Un-Vaccinated Animals

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Molalegne Bitew ◽  
Chintu Ravishankar ◽  
Soumendu Chakravarti ◽  
Gaurav Kumar Sharma ◽  
Sukdeb Nandi
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Protective Efficacy ◽  
Cell Immune Response ◽  
Respective Group ◽  
Cytokine Induction ◽  
Cell Mediated Immune Response ◽  
Significant Difference ◽  
The Mean

Recent invasion of multiple bluetongue virus serotypes (BTV) in different regions of the world necessitates urgent development of efficient vaccine that is directed against multiple BTV serotypes. In this experimental study, cell mediated immune response and protective efficacy of binary ethylenimine (BEI) inactivated Montanide™ ISA 206 adjuvanted pentavalent (BTV-1, 2, 10, 16 and 23) vaccine was evaluated in sheep and direct challenge with homologous BTV serotypes in their respective group. Significant (P<0.05) up-regulation of mRNA transcripts of IFN-α, IL-2, IL-6, IL-12, IFN-γ and TNF-α in PBMCs of vaccinated animals as compared to control (un-vaccinated) animals at certain time points was observed. On the other hand, there was a significant increase in mean ± SD percentage of CD8+ T cells after 7 days post challenge (DPC) but, the mean ± SD percentage of CD4+ T-cell population slightly declined at 7 DPC and enhanced after 14 DPC. Significant differences (P<0.05) of CD8+ and CD4+ T cells population was also observed between vaccinated and unvaccinated sheep. The vaccine also significantly (P<0.05) reduced BTV RNA load in PBMCs of vaccinated animals than unvaccinated animals following challenge. There were no significant difference (P>0.05) in cytokine induction, BTV RNA load and CD8+ and CD4+ cell count among BTV-1, 2, 10, 16 and 23 serotype challenges except significant increase in mean ± SD percentage of CD8+ in BTV-2 group. These findings put forwarded that binary ethylenimine inactivated montanide adjuvanted pentavalent bluetongue vaccine has stimulated cell mediated immune response and most importantly reduced the severity of BTV-1, 2, 10, 16 and 23 infections following challenge in respective group.

scholarly journals Absence of mucosal-associated invariant T cells in a person with a homozygous point mutation in MR1

2020 ◽  
Vol 5 (49) ◽  
pp. eabc9492 ◽  
Author(s):  
Lauren J. Howson ◽  
Wael Awad ◽  
Anouk von Borstel ◽  
Hui Jing Lim ◽  
Hamish E. G. McWilliam ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Protective Immunity ◽  
Bacterial Infections ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Mait Cells ◽  
History Of ◽  
Antigen Presenting ◽  
Mait Cell

The role unconventional T cells play in protective immunity in humans is unclear. Mucosal-associated invariant T (MAIT) cells are an unconventional T cell subset restricted to the antigen-presenting molecule MR1. Here, we report the discovery of a patient homozygous for a rare Arg31His (R9H in the mature protein) mutation in MR1 who has a history of difficult-to-treat viral and bacterial infections. MR1R9H was unable to present the potent microbially derived MAIT cell stimulatory ligand. The MR1R9H crystal structure revealed that the stimulatory ligand cannot bind due to the mutation lying within, and causing structural perturbation to, the ligand-binding domain of MR1. While MR1R9H could bind and be up-regulated by a MAIT cell inhibitory ligand, the patient lacked circulating MAIT cells. This shows the importance of the stimulatory ligand for MAIT cell selection in humans. The patient had an expanded γδ T cell population, indicating a compensatory interplay between these unconventional T cell subsets.

Tofacitinib modulates the VZV-specific CD4+ T cell immune response in vitro in lymphocytes of patients with rheumatoid arthritis

Rheumatology ◽  
2019 ◽  
Vol 58 (11) ◽  
pp. 2051-2060 ◽  
Author(s):  
Giovanni Almanzar ◽  
Felix Kienle ◽  
Marc Schmalzing ◽  
Anna Maas ◽  
Hans-Peter Tony ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Granzyme B ◽  
Janus Kinase ◽  
Cell Immune Response ◽  
Dependent Manner ◽  
Th1 Response

AbstractObjectiveRA is a chronic inflammatory disease characterized by lymphocyte infiltration and release of inflammatory cytokines. Previous studies have shown that treatment with Janus kinase inhibitors, such as tofacitinib, increased the incidence rate of herpes zoster compared with conventional DMARDs. Therefore, this study aimed to investigate the effect of tofacitinib on the varicella-zoster-virus (VZV)-specific T cell immune response.MethodsThe effect of tofacitinib on the VZV-specific T cell immune response was determined by evaluating the IFNγ production, the proliferative capacity, the VZV-induced differentiation into effector and memory T cells, the expression of activation marker CD69 and helper T cell type 1 (Th1)-characteristic chemokine receptors, such as CXCR3 and CCR5, as well as cytotoxic activity (perforin and granzyme B expression) of CD4+ T cells of patients with RA compared with healthy donors upon stimulation with VZV antigen in vitro.ResultsTofacitinib significantly reduced the IFNγ production, proliferation, activation, and CXCR3 expression of VZV-specific CD4+ T cells in a dose-dependent manner in short- and long-term lymphocyte culture. No effect on the distribution of naive, effectors or memory, or on the expression of perforin or granzyme B by VZV-specific CD4+ T cells was observed.ConclusionThis study showed that tofacitinib significantly modulated the Th1 response to VZV. The poor VZV-specific cellular immune response in patients with RA may be considered in recommendations regarding appropriate vaccination strategies for enhancing the VZV-specific Th1 response.

Sign in / Sign up

Export Citation Format

Share Document