scholarly journals Adenovirus serotype 5 vaccine vectors trigger IL-27-dependent inhibitory CD4+ T cell responses that impair CD8+ T cell function

2016 ◽  
Vol 1 (5) ◽  
pp. eaaf7643-eaaf7643 ◽  
Author(s):  
R. A. Larocca ◽  
N. M. Provine ◽  
M. Aid ◽  
M. J. Iampietro ◽  
E. N. Borducchi ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Vaccine Vectors ◽  
Adenovirus Serotype ◽  
Cell Responses ◽  
T Cell Function ◽  
Serotype 5

scholarly journals HIV-1-Specific Interleukin-21+ CD4+ T Cell Responses Contribute to Durable Viral Control through the Modulation of HIV-Specific CD8+ T Cell Function

2010 ◽  
Vol 85 (2) ◽  
pp. 733-741 ◽  
Author(s):  
M. F. Chevalier ◽  
B. Julg ◽  
A. Pyo ◽  
M. Flanders ◽  
S. Ranasinghe ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Viral Control ◽  
Cell Responses ◽  
T Cell Function ◽  
Interleukin 21 ◽  
Hiv 1

scholarly journals 306. CD8+ T-Cell Responses to Chronic Hepatitis C in Pregnancy

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S164-S164
Author(s):  
Stephanie Brooks ◽  
Samantha Coss ◽  
Christopher Walker ◽  
Jonathan Honegger
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Function ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Viral Control ◽  
Cell Responses ◽  
T Cell Function ◽  
Chronic Hcv ◽  
T Cell Help

Abstract Background Chronic hepatitis C virus (HCV) infection is marked by stable, high -level viremia and a failed T-cell response. HCV-specific CD4+ helper T cells are rare, and CD8+ cytotoxic T cells are functionally exhausted or ineffective due to viral escape mutations. Postpartum, a subset of infected women experience a substantial drop in viremia. Preliminary data indicate that this unusual viral decline may be linked to a resurgence of HCV-specific CD4+ T cells producing Th1 cytokines. How improved CD4+ helper T-cell function might affect viral replication in this scenario is not established. Here we tested the hypothesis that improved CD4+ T cell help mediates control of chronic HCV replication through enhanced CD8+ T-cell function. Methods We examined plasma HCV RNA viral load (VL) and HCV-specific T-cell responses in 33 women with chronic HCV during the third trimester (T3) and at 3 months postpartum (3P). HCV-specific CD4+ and CD8+ T-cell IL2 and IFNγ responses were measured by intracellular cytokine staining following stimulation of peripheral blood mononuclear cells with peptide pools corresponding to the HCV proteins NS3, NS4a, and NS4B. Results Median VL dropped from 5.87 log10 at T3 to 5.25 log10 at 3P (P < 0.0001, Wilcoxson signed rank), with a wide range from +0.4 log10 to -4.2 log10. The degree of decline correlated significantly with improved frequencies of HCV-specific CD4+ T cells producing IFNγ (P = 0.015 Spearman) but did not correlate with CD8+ T-cell changes. Nevertheless, improved T helper function correlated with increased HCV-specific CD8+ T-cell function (ΔCD4+IL2+ vs. ΔCD8+IFNγ+, P = 0.015 Spearman, graph 1; ΔCD4+IFNγ+ vs. CD8+IFNγ+ at 3P, P = 0.004 Spearman, graph 2). Conclusion Despite no significant association between virus-specific CD8+ T-cell Tc1 cytokine production and postpartum viral control, our data suggest that recovery of CD4+ T-cell help may augment CD8+ T-cell function. Further study incorporating viral genomic sequences to focus on intact class I epitopes is needed to clarify the relationship of improved CD8+ function and viral control in this unique model of immune restoration. Disclosures All authors: No reported disclosures.

scholarly journals Marburg virus survivor immune responses are Th1 skewed with limited neutralizing antibody responses

2017 ◽  
Vol 214 (9) ◽  
pp. 2563-2572 ◽  
Author(s):  
Spencer W. Stonier ◽  
Andrew S. Herbert ◽  
Ana I. Kuehne ◽  
Ariel Sobarzo ◽  
Polina Habibulin ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Ebola Virus ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Cd8 T Cell ◽  
Marburg Virus ◽  
Antibody Responses ◽  
Cd4 T Cell ◽  
Cell Responses

Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized. We report that immune responses in MARV survivors share characteristics with EBOV and SUDV infections but have some distinct differences. MARV survivors developed multivariate CD4+ T cell responses but limited CD8+ T cell responses, more in keeping with SUDV survivors than EBOV survivors. In stark contrast to SUDV survivors, rare neutralizing antibody responses in MARV survivors diminished rapidly after the outbreak. These results warrant serious consideration for any vaccine or therapeutic that seeks to be broadly protective, as different filoviruses may require different immune responses to achieve immunity.

scholarly journals Early CD4+ T Cell Responses Are Associated with Subsequent CD8+ T Cell Responses to an rAd5-Based Prophylactic Prime-Boost HIV Vaccine Strategy

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0152952 ◽  
Author(s):  
Edouard Lhomme ◽  
Laura Richert ◽  
Zoe Moodie ◽  
Chloé Pasin ◽  
Spyros A. Kalams ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Hiv Vaccine ◽  
Cd4 T Cell ◽  
Vaccine Strategy ◽  
Cell Responses

scholarly journals Single cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine

2021 ◽  
Author(s):  
Suhas Sureshchandra ◽  
Sloan A. Lewis ◽  
Brianna Doratt ◽  
Allen Jankeel ◽  
Izabela Ibraim ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Single Cell ◽  
Cd8 T Cells ◽  
Natural Infection ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Cell Responses

mRNA based vaccines for SARS-CoV-2 have shown exceptional clinical efficacy providing robust protection against severe disease. However, our understanding of transcriptional and repertoire changes following full vaccination remains incomplete. We used single-cell RNA sequencing and functional assays to compare humoral and cellular responses to two doses of mRNA vaccine with responses observed in convalescent individuals with asymptomatic disease. Our analyses revealed enrichment of spike-specific B cells, activated CD4 T cells, and robust antigen-specific polyfunctional CD4 T cell responses in all vaccinees. On the other hand, CD8 T cell responses were both weak and variable. Interestingly, clonally expanded CD8 T cells were observed in every vaccinee, as observed following natural infection. TCR gene usage, however, was variable, reflecting the diversity of repertoires and MHC polymorphism in the human population. Natural infection induced expansion of larger CD8 T cell clones occupied distinct clusters, likely due to the recognition of a broader set of viral epitopes presented by the virus not seen in the mRNA vaccine. Our study highlights a coordinated adaptive immune response where early CD4 T cell responses facilitate the development of the B cell response and substantial expansion of effector CD8 T cells, together capable of contributing to future recall responses.

scholarly journals Manipulation of Glucose Availability to Boost Cancer Immunotherapies

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2940
Author(s):  
Federica Marchesi ◽  
Debora Vignali ◽  
Beatrice Manini ◽  
Alessandra Rigamonti ◽  
Paolo Monti
Keyword(s):  
T Cell ◽  
Metabolic Regulation ◽  
Cell Function ◽  
Immune Cell ◽  
Deep Level ◽  
T Cell Responses ◽  
Cell Responses ◽  
T Cell Function ◽  
Cancer Tissues ◽  
Cancer Immunotherapies

The orchestration of T cell responses is intimately linked to the execution of metabolic processes, both in homeostasis and disease. In cancer tissues, metabolic alterations that characterize malignant transformation profoundly affect the composition of the immune microenvironment and the accomplishment of an effective anti-tumor response. The growing understanding of the metabolic regulation of immune cell function has shed light on the possibility to manipulate metabolic pathways as a strategy to improve T cell function in cancer. Among others, glucose metabolism through the glycolytic pathway is central in shaping T cell responses and emerges as an ideal target to improve cancer immunotherapy. However, metabolic manipulation requires a deep level of control over side-effects and development of biomarkers of response. Here, we summarize the metabolic control of T cell function and focus on the implications of metabolic manipulation for the design of immunotherapeutic strategies. Integrating our understanding of T cell function and metabolism will hopefully foster the forthcoming development of more effective immunotherapeutic strategies.

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