scholarly journals Functional Diversity of Cytomegalovirus–Specific T Cells Is Maintained in Older People and Significantly Associated With Protein Specificity and Response Size

2016 ◽  
Vol 214 (9) ◽  
pp. 1430-1437 ◽  
Author(s):  
Martha Bajwa ◽  
Serena Vita ◽  
Rosanna Vescovini ◽  
Martin Larsen ◽  
Paolo Sansoni ◽  
...  
Keyword(s):  
T Cells ◽  
Older People ◽  
Functional Diversity ◽  
Protein Specificity

scholarly journals Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients

2020 ◽  
Vol 17 (5) ◽  
pp. 541-543 ◽  
Author(s):  
Hong-Yi Zheng ◽  
Mi Zhang ◽  
Cui-Xian Yang ◽  
Nian Zhang ◽  
Xi-Cheng Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Functional Diversity ◽  
Peripheral Blood

scholarly journals Wnt/β-catenin activation epigenetically reprograms Regulatory T cells in IBD and progression to dysplasia.

2020 ◽  
Author(s):  
Fotini Gounari ◽  
Jasmin Quandt ◽  
Stephen Arnovitz ◽  
Leila Haghi ◽  
Janine Woehlk ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Regulatory T Cells ◽  
Functional Diversity ◽  
Bowel Disease ◽  
Elevated Expression ◽  
Inflammatory Bowel ◽  
Ifn Γ ◽  
Accessible Chromatin

Abstract The molecular and functional diversity of regulatory T-cells (Tregs) in health and in disease remains unclear. We previously described in colorectal cancer (CRC) patients a subpopulation of RORγt+ Tregs with elevated expression of β-catenin and pro-inflammatory properties. Here we observed progressive expansion of RORγt+ Tregs in inflammatory bowel disease (IBD) patients during inflammation and early dysplasia. Activating Wnt/β-catenin signaling in human and murine Tregs was sufficient to recapitulate the disease-associated increase in frequencies of RORγt+ Tregs expressing IL-17, IFN-γ, and TNFa. We found that binding of the β-catenin interacting partner, TCF-1, to DNA overlapped with Foxp3 binding at enhancer sites of pro-inflammatory pathway genes. Sustained Wnt/β-catenin activation induced newly accessible chromatin sites in these genes and upregulated their expression. These findings indicate that TCF-1 and Foxp3 together limit the expression of pro-inflammatory genes in Tregs. Activation of ꞵ-catenin signaling interferes with this function and promotes the disease-associated RORγt+ Treg phenotype.

scholarly journals Impaired Functional T-Cell Response to SARS-CoV-2 After Two Doses of BNT162b2 mRNA Vaccine in Older People

2021 ◽  
Vol 12 ◽  
Author(s):  
Julie Demaret ◽  
Bénédicte Corroyer-Simovic ◽  
Enagnon Kazali Alidjinou ◽  
Anne Goffard ◽  
Jacques Trauet ◽  
...  
Keyword(s):  
T Cells ◽  
Young Adults ◽  
T Cell ◽  
Antibody Response ◽  
Older People ◽  
Cell Response ◽  
T Cell Response ◽  
Term Care ◽  
Physiological Alterations ◽  
Antibody Titers

Long-term care facility (LTCF) older residents display physiological alterations of cellular and humoral immunity that affect vaccine responses. Preliminary reports suggested a low early postvaccination antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to focus on the specific T-cell response. We quantified S1-specific IgG, neutralizing antibody titers, total specific IFNγ-secreting T cells by ELISpot, and functionality of CD4+- and CD8+-specific T cells by flow cytometry, after two doses of the BNT162b2 vaccine in younger and older people, with and without previous COVID-19 infection (hereafter referred to as COVID-19-recovered and COVID-19-naive subjects, respectively). Frailty, nutritional, and immunosenescence parameters were collected at baseline in COVID-19-naive older people. We analyzed the immune response in 129 young adults (median age 44.0 years) and 105 older residents living in a LCTF (median age 86.5 years), 3 months after the first injection. Humoral and cellular memory responses were dramatically impaired in the COVID-19-naive older (n = 54) compared with the COVID-19-naive younger adults (n = 121). Notably, older participants’ neutralizing antibodies were 10 times lower than the younger’s antibody titers (p < 0.0001) and LCTF residents also had an impaired functional T-cell response: the frequencies of IFNγ+ and IFNγ+IL-2+TNFα+ cells among specific CD4+ T cells, and the frequency of specific CD8+ T cells were lower in COVID-19-naive older participants than in COVID-19-naive young adults (p < 0.0001 and p = 0.0018, respectively). However, COVID-19-recovered older participants (n = 51) had greater antibody and T-cell responses, including IFNγ+ and IFNγ+IL-2+TNFα+-specific CD4+ T cells (p < 0.0001), as well as TNFα+-specific CD8+ T cells (p < 0.001), than COVID-19-naive older adults. We also observed that “inflammageing” and particularly high plasma levels of TNFα was associated to poor antibody response in the older participants. In conclusion, our results show that the COVID-19-naive older people had low counts and impaired specific CD4+ and CD8+ T cells, in addition to impaired antibody response, and that specific studies are warranted to assess the efficiency of SARS-CoV-2 mRNA-based vaccines, as in other immunocompromised subjects. Our study also shows that, despite their physiological alterations of immunity, vaccination is highly efficient in boosting the prior natural memory response in COVID-19-recovered older people.

scholarly journals In-Depth Profiling of T-Cell Responsiveness to Commonly Recognized CMV Antigens in Older People Reveals Important Sex Differences

2021 ◽  
Vol 12 ◽  
Author(s):  
Bernhard Reus ◽  
Stefano Caserta ◽  
Martin Larsen ◽  
George Morrow ◽  
Aalia Bano ◽  
...  
Keyword(s):  
T Cells ◽  
Sex Differences ◽  
T Cell ◽  
Older People ◽  
Cd8 T Cells ◽  
Cell Response ◽  
T Cell Responses ◽  
T Cell Response ◽  
Cell Responses ◽  
Memory Subset

The impact of biological sex on T-cell immunity to Cytomegalovirus (CMV) has not been investigated in detail with only one published study comparing CMV-specific T-cell responses in men and women. Many studies, however, have shown an association between CMV infection and immunosenescence, with broad effects on peripheral blood lymphocyte subsets as well as the T and B-cell repertoires. Here, we provide a detailed analysis of CMV-specific T-cell responses in (n=94) CMV+ older people, including 47 women and 47 men aged between 60 and 93 years. We explore sex differences with respect to 16 different CMV proteins arranged in 14 peptide pools (overlapping peptides). Following ex vivo stimulation, CD4 and CD8 T-cells producing IFN-γ, TNF, and IL-2 were enumerated by flow-cytometry (intracellular cytokine staining). T-cell responses were evaluated in terms of each cytokine separately or in terms of cytokines produced simultaneously (polyfunctionality). Surface memory phenotype and CD3 downmodulation were assessed in parallel. The polyfunctionality index and a memory subset differentiation score were used to identify associations between response size, cytokine production, polyfunctionality, and memory subset distribution. While no significant sex differences were found with respect to overall CMV target protein selection, the T-cell response in men appeared more focused and accompanied by a more prominent accumulation of CMV-specific memory CD4 and CD8 T-cells. T-cell polyfunctionality and differentiation were similar in the sexes, however, CMV-specific T-cells in men produced more pro-inflammatory cytokines. Particularly, TNF production by CD4 T-cells was stronger in men than in women. Also, compared with women, men had larger responses to CMV proteins with immediate-early/early kinetics than women, which might have been driven by CMV reactivation. In conclusion, the CMV-specific T-cell response in men was larger and more pro-inflammatory than in women. Our findings may help explain sex differences in CMV-associated pathologies.

scholarly journals Self-reactivity controls functional diversity of naive CD8+ T cells by co-opting tonic type I interferon

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Young-Jun Ju ◽  
Sung-Woo Lee ◽  
Yoon-Chul Kye ◽  
Gil-Woo Lee ◽  
Hee-Ok Kim ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Functional Diversity ◽  
Type I Interferon ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Memory Cell ◽  
Cell Receptor ◽  
Receptor Interaction ◽  
Type I

AbstractThe strength of the T cell receptor interaction with self-ligands affects antigen-specific immune responses. However, the precise function and underlying mechanisms are unclear. Here, we demonstrate that naive CD8+ T cells with relatively high self-reactivity are phenotypically heterogeneous owing to varied responses to type I interferon, resulting in three distinct subsets, CD5loLy6C–, CD5hiLy6C–, and CD5hiLy6C+ cells. CD5hiLy6C+ cells differ from CD5loLy6C– and CD5hiLy6C– cells in terms of gene expression profiles and functional properties. Moreover, CD5hiLy6C+ cells demonstrate more extensive antigen-specific expansion upon viral infection, with enhanced differentiation into terminal effector cells and reduced memory cell generation. Such features of CD5hiLy6C+ cells are imprinted in a steady-state and type I interferon dependence is observed even for monoclonal CD8+ T cell populations. These findings demonstrate that self-reactivity controls the functional diversity of naive CD8+ T cells by co-opting tonic type I interferon signaling.

scholarly journals Cytomegalovirus-Specific T Cells Restricted by HLA-Cw*0702 Increase Markedly with Age and Dominate the CD8+ T-Cell Repertoire in Older People

2017 ◽  
Vol 8 ◽  
Author(s):  
Louise Hosie ◽  
Annette Pachnio ◽  
Jianmin Zuo ◽  
Hayden Pearce ◽  
Stanley Riddell ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Older People ◽  
Cd8 T Cell ◽  
T Cell Repertoire ◽  
Cell Repertoire

scholarly journals Influenza-Specific T Cells from Older People Are Enriched in the Late Effector Subset and Their Presence Inversely Correlates with Vaccine Response

PLoS ONE ◽  
2011 ◽  
Vol 6 (8) ◽  
pp. e23698 ◽  
Author(s):  
Lisa E. Wagar ◽  
Beth Gentleman ◽  
Hanspeter Pircher ◽  
Janet E. McElhaney ◽  
Tania H. Watts
Keyword(s):  
T Cells ◽  
Older People ◽  
Vaccine Response

scholarly journals Phenotypic and Functional Diversity in Regulatory T Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Louisa E. Sjaastad ◽  
David L. Owen ◽  
Sean I. Tracy ◽  
Michael A. Farrar
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Functional Diversity ◽  
Tissue Homeostasis ◽  
Treg Population ◽  
And Function ◽  
Environmental Antigens ◽  
Treg Development

The concept that a subset of T cells exists that specifically suppresses immune responses was originally proposed over 50 years ago. It then took the next 30 years to solidify the concept of regulatory T cells (Tregs) into the paradigm we understand today – namely a subset of CD4+ FOXP3+ T-cells that are critical for controlling immune responses to self and commensal or environmental antigens that also play key roles in promoting tissue homeostasis and repair. Expression of the transcription factor FOXP3 is a defining feature of Tregs, while the cytokine IL2 is necessary for robust Treg development and function. While our initial conception of Tregs was as a monomorphic lineage required to suppress all types of immune responses, recent work has demonstrated extensive phenotypic and functional diversity within the Treg population. In this review we address the ontogeny, phenotype, and function of the large number of distinct effector Treg subsets that have been defined over the last 15 years.

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