scholarly journals Differential impact of self and environmental antigens on the ontogeny and maintenance of CD4+ T cell memory

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Thea Hogan ◽  
Maria Nowicka ◽  
Daniel Cownden ◽  
Claire F Pearson ◽  
Andrew J Yates ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
T Cell Memory ◽  
Effector Memory ◽  
Laboratory Mice ◽  
Differential Impact ◽  
Persistent Memory ◽  
Environmental Antigens ◽  
Memory Cd4 T Cells

Laboratory mice develop populations of circulating memory CD4+ T cells in the absence of overt infection. We have previously shown that these populations are replenished from naive precursors at high levels throughout life (Gossel et al., 2017). However, the nature, relative importance and timing of the forces generating these cells remain unclear. Here, we tracked the generation of memory CD4+ T cell subsets in mice housed in facilities differing in their ‘dirtiness’. We found evidence for sequential naive to central memory to effector memory development, and confirmed that both memory subsets are heterogeneous in their rates of turnover. We also inferred that early exposure to self and environmental antigens establishes persistent memory populations at levels determined largely, although not exclusively, by the dirtiness of the environment. After the first few weeks of life, however, these populations are continuously supplemented by new memory cells at rates that are independent of environment.

scholarly journals Differential impact of self and environmental antigens on the ontogeny and maintenance of CD4+ T cell memory

2019 ◽  
Author(s):  
Thea Hogan ◽  
Maria Nowicka ◽  
Daniel Cownden ◽  
Claire Pearson ◽  
Andrew J. Yates ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Subsets ◽  
T Cell Memory ◽  
Effector Memory ◽  
Relative Importance ◽  
Early Exposure ◽  
Laboratory Mice ◽  
Differential Impact ◽  
Persistent Memory ◽  
Environmental Antigens

AbstractLaboratory mice develop populations of circulating memory CD4+ T cells in the absence of overt infection. We have previously shown that these populations are replenished from naive precursors at high levels throughout life (Gossel et al., 2017). However, the nature, relative importance and timing of the forces generating these cells remain unclear. Here, we tracked the generation of memory CD4+ T cell subsets in mice housed in facilities differing in their ‘dirtiness’. We found evidence for sequential naive to central memory to effector memory development, and confirmed that both memory subsets are heterogeneous in their rates of turnover. We also inferred that early exposure to self and environmental antigens establishes persistent memory populations at levels determined largely, though not exclusively, by the dirtiness of the environment. After the first few weeks of life, however, these populations are continuously supplemented by new memory cells at rates that are independent of environment.

scholarly journals Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Graeme Gossel ◽  
Thea Hogan ◽  
Daniel Cownden ◽  
Benedict Seddon ◽  
Andrew J Yates
Keyword(s):  
T Cells ◽  
T Cell ◽  
De Novo ◽  
Memory Cell ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
T Cell Memory ◽  
Cell Memory ◽  
Quiescent Cells ◽  
Memory Cd4 T Cells

Characterising the longevity of immunological memory requires establishing the rules underlying the renewal and death of peripheral T cells. However, we lack knowledge of the population structure and how self-renewal and de novo influx contribute to the maintenance of memory compartments. Here, we characterise the kinetics and structure of murine CD4 T cell memory subsets by measuring the rates of influx of new cells and using detailed timecourses of DNA labelling that also distinguish the behaviour of recently divided and quiescent cells. We find that both effector and central memory CD4 T cells comprise subpopulations with highly divergent rates of turnover, and show that inflows of new cells sourced from the naive pool strongly impact estimates of memory cell lifetimes and division rates. We also demonstrate that the maintenance of CD4 T cell memory subsets in healthy mice is unexpectedly and strikingly reliant on this replenishment.

scholarly journals Author response: Differential impact of self and environmental antigens on the ontogeny and maintenance of CD4+ T cell memory

2019 ◽  
Author(s):  
Thea Hogan ◽  
Maria Nowicka ◽  
Daniel Cownden ◽  
Claire F Pearson ◽  
Andrew J Yates ◽  
...  
Keyword(s):  
T Cell ◽  
Cd4 T Cell ◽  
Author Response ◽  
T Cell Memory ◽  
Differential Impact ◽  
Cell Memory ◽  
Environmental Antigens

scholarly journals 343. T-cell Subsets Associated with Diabetes in Veterans with and without HIV

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S182-S183
Author(s):  
Samuel Bailin ◽  
Kathleen McGinnis ◽  
Wyatt J McDonnell ◽  
Kaku So-Armah ◽  
Melissa Wellons ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Immune Activation ◽  
Cd4 T Cells ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Hiv Status ◽  
Adaptive Immune ◽  
Memory Cd4 T Cells

Abstract Background Depletion of naïve CD4+ T cells and elevated adaptive immune activation are hallmarks of HIV infection. Higher proportions of memory CD4+ T cells are associated with prevalent diabetes in the general population, but few studies of persons with HIV (PWH) exist. Methods We analyzed data from 1532 PWH and 836 uninfected veterans in the longitudinal Veterans Aging Cohort Study (VACS), which archived peripheral mononuclear cells from these veterans between 2005 and 2007. We used flow cytometry to phenotype CD4+ and CD8+ T cells, including naïve, activated CD38+, senescent CD57+, total memory, and memory subsets. Prevalent diabetes (at blood collection) was identified in the VA electronic medical record using random glucose, hemoglobin A1c, ICD-9 codes, and medication. Cases were validated by two-physician chart review. We used multivariate logistic regression models adjusted for age, gender, body mass index, race/ethnicity, unhealthy alcohol use, hepatitis C, CMV status, and viral suppression stratified by HIV status to identify T-cell subsets associated with diabetes in PWH and uninfected. Results The cohort was 95% male, 68% African-American, and 22% diabetic. Higher CD4+CD45RO+ memory T cells were associated with prevalent diabetes in the uninfected and in PWH (P = 0.03 and P = 0.07, respectively; Figure A). Among subsets, diabetes was associated with higher transitional memory CD4+ T cells in the uninfected (P = 0.01), but higher central memory cells (P = 0.02) and lower effector memory cells (P = 0.04) in PWH. T effector memory RA+ cells were not associated with diabetes. Lower senescent CD4+CD57+ T cells were associated with diabetes in both PWH and uninfected (P = 0.03 and P = 0.04, respectively; Figure B), but results for naïve CD8+ T cells diverged: diabetes was associated with higher naïve CD8+cells in PWH but lower in uninfected (P = 0.01 and P < 0.01, respectively; Figure C). We assessed interaction by HIV status in a pooled model, which was only significant for the naïve CD8+ T cells (P = 0.01). Conclusion The adaptive immune profile associated with prevalent diabetes was similar by HIV status and characterized by a shift in CD4+ T cells from senescent to memory phenotypes, suggesting that chronic immune activation contributes to the higher risk of diabetes in PWH. Disclosures All authors: No reported disclosures.

scholarly journals Human CD4+ central and effector memory T cells produce IL-21: effect on cytokine-driven proliferation of CD4+ T cell subsets

2007 ◽  
Vol 19 (10) ◽  
pp. 1191-1199 ◽  
Author(s):  
T. Onoda ◽  
M. Rahman ◽  
H. Nara ◽  
A. Araki ◽  
K. Makabe ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Effector Memory ◽  
Effector Memory T Cells

scholarly journals ROLE OF DISTINCT CD4+ T-CELL SUBSETS IN HIV-INFECTION PATHOGENESIS

2020 ◽  
pp. 236-246
Author(s):  
E. V. Saidakova ◽  
Keyword(s):  
Immune System ◽  
T Cell ◽  
T Lymphocytes ◽  
Hiv Infection ◽  
T Lymphocyte ◽  
Highly Active Antiretroviral Therapy ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Effector Memory ◽  
T Lymphocyte Subsets

CD4+ T-cell pool is composed of cells residing in different maturation stages. Naive CD4+ T-lymphocytes, CD4+ stem memory T-cells, CD4+ central and effector memory T-lymphocytes perform var-ious functions in maintaining the immune system homeostasis. Despite phenotypic differences, each of those cells can be infected with HIV. Specific features of distinct CD4+ T-lymphocyte subsets determine their role in HIV-infection pathogenesis. By analyzing changes of CD4+ T-lymphocyte subset composi-tion, one can estimate the degree of the immune system damage and make predictions of immune recov-ery under highly active antiretroviral therapy. The article summarizes the main events occurring with CD4+ T-cell subsets during HIV-infection.

scholarly journals Anti-apoptotic clone 11 derived peptides induce in vitro death of CD4+ T cells susceptible to HIV-1 infection

2020 ◽  
Author(s):  
Anastassia Mikhailova ◽  
José Carlos Valle-Casuso ◽  
Annie David ◽  
Valérie Monceaux ◽  
Stevenn Volant ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
T Cell Memory ◽  
Target Cells ◽  
Cell Memory ◽  
Infected Cells ◽  
Hiv 1

ABSTRACTHIV-1 successfully establishes long-term infection in its target cells despite viral cytotoxic effects. We have recently shown that cell metabolism is an important factor driving CD4+ T-cell susceptibility to HIV-1 and the survival of infected cells. We show here that expression of anti-apoptotic clone 11 (AAC-11), an anti-apoptotic factor upregulated in many cancers, increased with progressive CD4+ T cell memory differentiation in association with the expression of cell cycle, activation and metabolism genes and correlated with susceptibility to HIV-1 infection. Synthetic peptides based on the LZ domain sequence of AAC-11, responsible for its interaction with molecular partners, were previously shown to be cytotoxic to cancer cells. Here we observed that these peptides also blocked HIV-1 infection by inducing cell death of HIV-1 susceptible primary CD4+ T-cells across all T-cell subsets. The peptides targeted metabolically active cells and had the greatest effect on effector and transitional CD4+ T cell memory subsets. Our results suggest that AAC-11 survival pathway is potentially involved in the survival of HIV-1 infectable cells and provide a proof of principle that some cellular characteristics can be targeted to eliminate the cells offering the best conditions to sustain HIV-1 replication.IMPORTANCEAlthough antiretroviral treatment efficiently blocks HIV multiplication, it cannot eliminate the cells already carrying integrated proviruses. In the search for a HIV cure the identification of new potential targets to selectively eliminate infected cells is of the outmost importance. We show here that peptides derived from the anti-apoptotic clone 11 (AAC-11), which expression levels correlated with susceptibility to HIV-1 infection of CD4+ T-cells, induced cytotoxicity in CD4+ T-cells showing the highest levels of activation and metabolic activity, conditions known to favor HIV-1 infection. Accordingly, CD4+ T-cells that survived the cytotoxic action of the AAC-11 peptides were resistant to HIV-1 replication. Our results identify a new potential molecular pathway to target HIV-1 infection.

scholarly journals Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4+ T cells

2012 ◽  
Vol 209 (13) ◽  
pp. 2383-2394 ◽  
Author(s):  
Atsushi Nishida ◽  
Kiyotaka Nagahama ◽  
Hirotsugu Imaeda ◽  
Atsuhiro Ogawa ◽  
Cindy W. Lau ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cell Expansion ◽  
Intestinal Inflammation ◽  
Cd4 T Cell ◽  
Effector Memory ◽  
Glycan Structure ◽  
T Cell Expansion ◽  
Memory Cd4 T Cells

Immune responses are modified by a diverse and abundant repertoire of carbohydrate structures on the cell surface, which is known as the glycome. In this study, we propose that a unique glycome that can be identified through the binding of galectin-4 is created on local, but not systemic, memory CD4+ T cells under diverse intestinal inflammatory conditions, but not in the healthy state. The colitis-associated glycome (CAG) represents an immature core 1–expressing O-glycan. Development of CAG may be mediated by down-regulation of the expression of core-2 β1,6-N-acetylglucosaminyltransferase (C2GnT) 1, a key enzyme responsible for the production of core-2 O-glycan branch through addition of N-acetylglucosamine (GlcNAc) to a core-1 O-glycan structure. Mechanistically, the CAG seems to contribute to super raft formation associated with the immunological synapse on colonic memory CD4+ T cells and to the consequent stabilization of protein kinase C θ activation, resulting in the stimulation of memory CD4+ T cell expansion in the inflamed intestine. Functionally, CAG-mediated CD4+ T cell expansion contributes to the exacerbation of T cell–mediated experimental intestinal inflammations. Therefore, the CAG may be an attractive therapeutic target to specifically suppress the expansion of effector memory CD4+ T cells in intestinal inflammation such as that seen in inflammatory bowel disease.

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