scholarly journals Protracted yet coordinated differentiation of long-lived SARS-CoV-2-specific CD8+ T cells during COVID-19 convalescence

2021 ◽  
Author(s):  
Tongcui Ma ◽  
Heeju Ryu ◽  
Matthew McGregor ◽  
Benjamin Babcock ◽  
Jason Neidleman ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cell ◽  
Homeostatic Proliferation ◽  
State Characteristic ◽  
Detailed Characterization ◽  
Central Memory T Cells ◽  
Lymph Node Homing ◽  
Proliferation Potential

ABSTRACTCD8+ T cells are important antiviral effectors that can potentiate long-lived immunity against COVID-19, but a detailed characterization of these cells has been hampered by technical challenges. We screened 21 well-characterized, longitudinally-sampled convalescent donors that recovered from mild COVID-19 against a collection of SARS-CoV-2 tetramers, and identified one participant with an immunodominant response against Nuc322-331, a peptide that is conserved in all the SARS-CoV-2 variants-of-concern reported to date. We conducted 38- parameter CyTOF phenotyping on tetramer-identified Nuc322-331-specific CD8+ T cells, and on CD4+ and CD8+ T cells recognizing the entire nucleocapsid and spike proteins from SARS- CoV-2, and took 32 serological measurements on longitudinal specimens from this participant. We discovered a coordination of the Nuc322-331-specific CD8+ T response with both the CD4+ T cell and antibody pillars of adaptive immunity. Nuc322-331-specific CD8+ T cells were predominantly central memory T cells, but continually evolved over a ∼6-month period of convalescence. We observed a slow and progressive decrease in the activation state and polyfunctionality of the Nuc322-331-specific CD8+ T cells, accompanied by an increase in their lymph-node homing and homeostatic proliferation potential. These results suggest that following a typical case of mild COVID-19, SARS-CoV-2-specific CD8+ T cells not only persist but continuously differentiate in a coordinated fashion well into convalescence, into a state characteristic of long-lived, self-renewing memory.

scholarly journals Detailed characterization of human Mycobacterium tuberculosis specific HLA-E restricted CD8+ T cells

2017 ◽  
Vol 48 (2) ◽  
pp. 293-305 ◽  
Author(s):  
Teresa Prezzemolo ◽  
Krista E. van Meijgaarden ◽  
Kees L.M.C. Franken ◽  
Nadia Caccamo ◽  
Francesco Dieli ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Cd8 T Cells ◽  
Detailed Characterization

Lymphopenia-Associated CD4+ T Cell-Mediated Colitis Correlates with Homeostatic but Not with Endogenous Proliferation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1314-1314
Author(s):  
Christian Blank ◽  
Kerstin Schuster ◽  
Reinhard Andreesen ◽  
Andreas Mackensen
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Chronic Inflammatory Bowel Disease ◽  
Target Cells ◽  
Homeostatic Proliferation ◽  
Cfse Dilution ◽  
Peripheral T Cells

Abstract Transfer of peripheral T cells into lymphopenic hosts results in a burst-like proliferation, called endogenous proliferation (EP) and an antigen-independent proliferation, called homeostatic proliferation (HP). Formerly both were named lymphopenic or homeostatic proliferation. T cells that undergo either endogenous or homeostatic proliferation acquire an activated phenotype, develop the ability to produce Interferon-gamma (IFN-g) and to lyse target cells specifically, but only homeostatic proliferating T cells acquire a CD44bright CD62Lbright phenotype. We developed a murine model to distinguish effects of both types of lymphopenia-associated proliferation. In this model we were able to induce polyclonal populations of syngenic CD4+ or CD8+ peripheral T cells (derived from C57BL/6 mice) to proliferate homeostatically (after transfer into lymphopenic RAG−/− mice) whereas only EP occurred when transferring into mice that inherit only an additional single CD8+ T cell clone (transfer into the non-lymphopenic P14/RAG−/− mice). CFSE dilution was observed from CD4+ or CD8+ T cells transferred into RAG−/− mice, whereas HP was inhibited when transferring the same cells into P14/RAG−/− mice, whereas EP occurred in both recipients. Independent of CFSE dilution T cells developed CD44bright phenotype after transfer into RAG−/− as well as in P14/RAG−/− mice as early as day 5, whereas the host P14tg CD8+ clone kept its naïve phenotype. Applying our model on the CD4+ T-cell-induced colitis model, we found HP to play a pivotal role in induction of colitis. Despite the notion of EP being triggered by antigens from the bowel, colitis was only induced when HP occurred, independent of the occurrence of EP. In detail CD4+ T cells induced colitis 10 weeks after transfer into RAG−/− mice (EP and HP). However neither RAG−/− mice transplanted with CD8+ T cells nor P14/RAG−/− mice transplanted with CD4+ T cells (only EP) developed any signs of colitis. In addition the treatment with or without antibiotics during these 10 weeks did not influence on the induction of colitis. We therefore conclude that the lymphopenia-mediated colitis after transfer of polyclonal CD4+ T cells correlates only with the occurrence of homeostatic proliferation. Furthermore the absence of regulatory CD4+CD25+ T cells within the suppressing P14 tg CD8+ clone indicates HP-induced colitis to be mediated by competition for cytokines or self-MHC stimulus. These findings might be of important relevance for research concerning chronic inflammatory bowel disease and donor lymphocyte induced colitis.

Characterization of HLA-A*0201 restricted cytotoxic CD8+ T cells directed against ewing tumor specific antigens

2009 ◽  
Vol 221 (03) ◽  
Author(s):  
S Pirson ◽  
U Thiel ◽  
H Bernhard ◽  
GHS Richter ◽  
S Burdach
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Specific Antigens ◽  
Ewing Tumor

scholarly journals Longitudinal Changes in Cd4+, Cd8+ T Cell Phenotype and Activation Marker Expression Following Antiretroviral Therapy Initiation among Patients with Cryptococcal Meningitis

2019 ◽  
Vol 5 (3) ◽  
pp. 63
Author(s):  
Alice Bayiyana ◽  
Samuel Okurut ◽  
Rose Nabatanzi ◽  
Godfrey Zziwa ◽  
David R. Boulware ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Surface ◽  
Cd8 T Cells ◽  
Cryptococcal Meningitis ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Effector Memory ◽  
Memory Subset

Despite improvement in the prognosis of HIV/AIDS (human immunodeficiency virus/acquired immune deficiency syndrome) patients on antiretroviral therapy (ART), cryptococcal meningitis (CM) still causes 10–15% mortality among HIV-infected patients. The immunological impact of ART on the CD4+ and CD8+ T cell repertoire during cryptococcal co-infection is unclear. We determined longitudinal phenotypic changes in T cell subsets among patients with CM after they initiated ART. We hypothesized that ART alters the clonotypic phenotype and structural composition of CD4+ and CD8+ T cells during CM co-infection. For this substudy, peripheral blood mononuclear cells (PBMC) were isolated at four time points from CM patients following ART initiation during the parent study (ClinicalTrials.gov number, NCT01075152). Phenotypic characterization of CD4+ and CD8+ T cells was done using T cell surface marker monoclonal antibodies by flow cytometry. There was variation in the expression of immunophenotypic markers defining central memory (CD27+CD45R0+), effector memory (CD45R0+CD27–), immune activation (CD38+ and Human Leucocyte Antigen DR (HLA-DR+), and exhaustion (Programmed cell death protein one (PD-1) in the CD4+ T cell subset. In comparison to the CD4+ T cell population, the CD8+ central memory subset declined gradually with minimal increase in the effector memory subset. Both CD4+ and CD8+ T cell immune exhaustion and activation markers remained elevated over 12 weeks. The relative surge and decline in the expression of T cell surface markers outlines a variation in the differentiation of CD4+ T cells during ART treatment during CM co-infection.

scholarly journals Reduced immune-regulatory molecule expression on human colonic memory CD4 T cells in older adults

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Stephanie M. Dillon ◽  
Tezha A. Thompson ◽  
Allison J. Christians ◽  
Martin D. McCarter ◽  
Cara C. Wilson
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Older Persons ◽  
Age Groups ◽  
T Cell Immunity ◽  
Cd4 T Cell ◽  
Cell Immunity ◽  
Memory Cd4 T Cells

Abstract Background The etiology of the low-level chronic inflammatory state associated with aging is likely multifactorial, but a number of animal and human studies have implicated a functional decline of the gastrointestinal immune system as a potential driver. Gut tissue-resident memory T cells play critical roles in mediating protective immunity and in maintaining gut homeostasis, yet few studies have investigated the effect of aging on human gut T cell immunity. To determine if aging impacted CD4 T cell immunity in the human large intestine, we utilized multi-color flow cytometry to measure colonic lamina propria (LP) CD4 T cell frequencies and immune-modulatory marker expression in younger (mean ± SEM: 38 ± 1.5 yrs) and older (77 ± 1.6 yrs) adults. To determine cellular specificity, we evaluated colon LP CD8 T cell frequency and phenotype in the same donors. To probe tissue specificity, we evaluated the same panel of markers in peripheral blood (PB) CD4 T cells in a separate cohort of similarly aged persons. Results Frequencies of colonic CD4 T cells as a fraction of total LP mononuclear cells were higher in older persons whereas absolute numbers of colonic LP CD4 T cells per gram of tissue were similar in both age groups. LP CD4 T cells from older versus younger persons exhibited reduced CTLA-4, PD-1 and Ki67 expression. Levels of Bcl-2, CD57, CD25 and percentages of activated CD38+HLA-DR+ CD4 T cells were similar in both age groups. In memory PB CD4 T cells, older age was only associated with increased CD57 expression. Significant age effects for LP CD8 T cells were only observed for CTLA-4 expression, with lower levels of expression observed on cells from older adults. Conclusions Greater age was associated with reduced expression of the co-inhibitory receptors CTLA-4 and PD-1 on LP CD4 T cells. Colonic LP CD8 T cells from older persons also displayed reduced CTLA-4 expression. These age-associated profiles were not observed in older PB memory CD4 T cells. The decline in co-inhibitory receptor expression on colonic LP T cells may contribute to local and systemic inflammation via a reduced ability to limit ongoing T cell responses to enteric microbial challenge.

scholarly journals HIV-Related Arterial Stiffness in Malawian Adults Is Associated With the Proportion of PD-1–Expressing CD8+ T Cells and Reverses With Antiretroviral Therapy

2019 ◽  
Vol 219 (12) ◽  
pp. 1948-1958 ◽  
Author(s):  
Christine Kelly ◽  
Henry C Mwandumba ◽  
Robert S Heyderman ◽  
Kondwani Jambo ◽  
Raphael Kamng’ona ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Arterial Stiffness ◽  
Cell Count ◽  
Cd8 T Cells ◽  
Sub Saharan Africa ◽  
Cd4 T Cell ◽  
Sub Saharan ◽  
Cd4 T Cell Count

Abstract Background The contribution of immune activation to arterial stiffness and its reversibility in human immunodeficiency virus (HIV)–infected adults in sub-Saharan Africa is unknown. Methods HIV-uninfected and HIV-infected Malawian adults initiating antiretroviral therapy (ART) with a CD4+ T-cell count of <100 cells/μL were enrolled and followed for 44 weeks; enrollment of infected adults occurred 2 weeks after ART initiation. We evaluated the relationship between carotid femoral pulse wave velocity (cfPWV) and T-cell activation (defined as HLA-DR+CD38+ T cells), exhaustion (define as PD-1+ T cells), and senescence (defined as CD57+ T cells) and monocyte subsets, using normal regression. Results In 279 HIV-infected and 110 HIV-uninfected adults, 142 (37%) had hypertension. HIV was independently associated with a 12% higher cfPWV (P = .02) at baseline and a 14% higher cfPWV at week 10 (P = .02), but the increases resolved by week 22. CD4+ and CD8+ T-cell exhaustion were independently associated with a higher cfPWV at baseline (P = .02). At 44 weeks, arterial stiffness improved more in those with greater decreases in the percentage of CD8+ T cells and the percentage of PD-1+CD8+ T cells (P = .01 and P = .03, respectively). When considering HIV-infected participants alone, the adjusted arterial stiffness at week 44 tended to be lower in those with higher baseline percentage of PD-1+CD8+ T cells (P = .054). Conclusions PD-1+CD8+ T-cells are associated with HIV-related arterial stiffness, which remains elevated during the first 3 months of ART. Resources to prevent cardiovascular disease in sub-Saharan Africa should focus on blood pressure reduction and individuals with a low CD4+ T-cell count during early ART.

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