scholarly journals Premature CD4+ T Cell Aging and Its Contribution to Lymphopenia-Induced Proliferation of Memory Cells in Autoimmune-Prone Non-Obese Diabetic Mice

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e89379 ◽  
Author(s):  
Ting-Ting Sheu ◽  
Bor-Luen Chiang ◽  
Jui-Hung Yen ◽  
Wen-Chi Lin
Keyword(s):  
T Cell ◽  
Cd4 T Cell ◽  
Cell Aging ◽  
Memory Cells ◽  
Diabetic Mice

scholarly journals HIV-1 Viremia Prevents the Establishment of Interleukin 2–producing HIV-specific Memory CD4+ T Cells Endowed with Proliferative Capacity

2003 ◽  
Vol 198 (12) ◽  
pp. 1909-1922 ◽  
Author(s):  
Souheil-Antoine Younes ◽  
Bader Yassine-Diab ◽  
Alain R. Dumont ◽  
Mohamed-Rachid Boulassel ◽  
Zvi Grossman ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Memory Cells ◽  
Cell Responses ◽  
Specific Memory ◽  
Ifn Γ ◽  
Memory Cd4 T Cells

CD4+ T cell responses are associated with disease control in chronic viral infections. We analyzed human immunodeficiency virus (HIV)-specific responses in ten aviremic and eight viremic patients treated during primary HIV-1 infection and for up to 6 yr thereafter. Using a highly sensitive 5-(and-6)-carboxyfluorescein diacetate-succinimidyl ester–based proliferation assay, we observed that proliferative Gag and Nef peptide-specific CD4+ T cell responses were 30-fold higher in the aviremic patients. Two subsets of HIV-specific memory CD4+ T cells were identified in aviremic patients, CD45RA− CCR7+ central memory cells (Tcm) producing exclusively interleukin (IL)-2, and CD45RA− CCR7− effector memory cells (Tem) that produced both IL-2 and interferon (IFN)-γ. In contrast, in viremic, therapy-failing patients, we found significant frequencies of Tem that unexpectedly produced exclusively IFN-γ. Longitudinal analysis of HIV epitope–specific CD4+ T cells revealed that only cells that had the capacity to produce IL-2 persisted as long-term memory cells. In viremic patients the presence of IFN-γ–producing cells was restricted to periods of elevated viremia. These findings suggest that long-term CD4+ T cell memory depends on IL-2–producing CD4+ T cells and that IFN-γ only–producing cells are short lived. Our data favor a model whereby competent HIV-specific Tcm continuously arise in small numbers but under persistent antigenemia are rapidly induced to differentiate into IFN-γ only–producing cells that lack self-renewal capacity.

scholarly journals Rapid default transition of CD4 T cell effectors to functional memory cells

2007 ◽  
Vol 204 (9) ◽  
pp. 2199-2211 ◽  
Author(s):  
K. Kai McKinstry ◽  
Susanne Golech ◽  
Won-Ha Lee ◽  
Gail Huston ◽  
Nan-Ping Weng ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cd4 T Cell ◽  
Effector Memory ◽  
Memory Cells ◽  
Two Stages

The majority of highly activated CD4 T cell effectors die after antigen clearance, but a small number revert to a resting state, becoming memory cells with unique functional attributes. It is currently unclear when after antigen clearance effectors return to rest and acquire important memory properties. We follow well-defined cohorts of CD4 T cells through the effector-to-memory transition by analyzing phenotype, important functional properties, and gene expression profiles. We find that the transition from effector to memory is rapid in that effectors rested for only 3 d closely resemble canonical memory cells rested for 60 d or longer in the absence of antigen. This is true for both Th1 and Th2 lineages, and occurs whether CD4 T cell effectors rest in vivo or in vitro, suggesting a default pathway. We find that the effector–memory transition at the level of gene expression occurs in two stages: a rapid loss of expression of a myriad of effector-associated genes, and a more gradual gain of expression of a cohort of genes uniquely associated with memory cells rested for extended periods.

scholarly journals Telomere and ATM Dynamics in CD4 T-Cell Depletion in Active and Virus-Suppressed HIV Infections

2020 ◽  
Vol 94 (22) ◽  
Author(s):  
Sushant Khanal ◽  
Qiyuan Tang ◽  
Dechao Cao ◽  
Juan Zhao ◽  
Lam Nhat Nguyen ◽  
...  
Keyword(s):  
Dna Damage ◽  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Cell Apoptosis ◽  
Cd4 T Cells ◽  
Molecular Mechanisms ◽  
Cd4 T Cell ◽  
Cell Aging

ABSTRACT CD4 T-cell depletion is a hallmark of HIV/AIDS, but the underlying mechanism is still unclear. We have recently shown that ataxia-telangiectasia-mutated (ATM) deficiency in CD4 T cells accelerates DNA damage, telomere erosion, and cell apoptosis in HIV-infected individuals on antiretroviral therapy (ART). Whether these alterations in ART-treated HIV subjects occur in vitro in HIV-infected CD4 T cells remains unknown. In this study, we employed a cellular model of HIV infection to characterize the mechanisms underlying CD4 T-cell destruction by analyzing the telomeric DNA damage response (DDR) and cellular apoptosis in highly permissive SupT1 cells, followed by the validation of our observations in primary CD4 T cells with active or drug-suppressed HIV infection. Specifically, we established an in vitro HIV T-cell culture system with viral replication and raltegravir (RAL; an integrase inhibitor) suppression, mimicking active and ART-controlled HIV infection in vivo. We demonstrated that HIV-induced, telomeric DDR plays a pivotal role in triggering telomere erosion, premature T-cell aging, and CD4 T-cell apoptosis or depletion via dysregulation of the PI3K/ATM pathways. This in vitro model provides a new tool to investigate HIV pathogenesis, and our results shed new light on the molecular mechanisms of telomeric DDR and CD4 T-cell homeostasis during HIV infection. IMPORTANCE The hallmark of HIV infection is a gradual depletion of CD4 T cells, with a progressive decline of host immunity. How CD4 T cells are depleted in individuals with active and virus-suppressed HIV infection remains unclear. In this study, we employed a cellular model of HIV infection to characterize the mechanisms underlying CD4 T-cell destruction by analyzing the chromosome end (telomere) DNA damage response (DDR) and cellular apoptosis in a T-cell line (highly permissive SupT1 cells), as well as in primary CD4 T cells with active or drug-suppressed HIV infection. We demonstrated that HIV-induced telomeric DDR plays a critical role in inducing telomere loss, premature cell aging, and CD4 T-cell apoptosis or depletion via dysregulation of the PI3K/ATM pathways. This study sheds new light on the molecular mechanisms of telomeric DDR and its role in CD4 T-cell homeostasis during HIV infection.

Antiparasitic and immunomodulating effects of nitazoxanide, ivermectin and selenium on Cryptosporidium infection in diabetic mice

2021 ◽  
Vol 30 (4) ◽  
Author(s):  
Mennat-Elrahman Ahmed Fahmy ◽  
Amany Ahmed Abdelaal ◽  
Soad Ismail Hassan ◽  
Maisa Ahmed Shalaby ◽  
Mousa Abdelgawad Mousa Ismail ◽  
...  
Keyword(s):  
T Cell ◽  
Combined Therapy ◽  
Treatment Strategies ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Cryptosporidium Infection ◽  
Diabetic Mice ◽  
Cell Ratio ◽  
Treatment Regimens ◽  
Cell Expression

Abstract The present work aims to investigate the antiparasitic and the immunomodulating effects of nitazoxanide (NTZ) and ivermectin (IVC) alone or combined together or combined with selenium (Se), on Cryptosporidium infection in diabetic mice. The results revealed that the combined NTZ and IVC therapy achieved the highest reduction of fecal oocysts (92%), whereas single NTZ showed the lowest reduction (63%). Also, adding Se to either NTZ or IVC resulted in elevation of oocyst reduction from 63% to 71% and from 82% to 84% respectively. All treatment regimens, with the exception of NTZ monotherapy, showed a significant improvement in the intestinal histopathology, the highest score was in combined NTZ and IVC therapy. The unique results of immunohistochemistry in this study showed reversal of the normal CD4/CD8 T cell ratio in the infected untreated mice, however, following therapy it reverts back to a normal balanced ratio. The combined (NTZ+ IVC) treatment demonstrated the highest level of CD4 T cell expression. Taken together, NTZ and IVC combined therapy showed remarkable anti-parasitic and immunostimulatory effects, specifically towards the CD4 population that seem to be promising in controlling cryptosporidiosis in diabetic individuals. Further research is required to explore other effective treatment strategies for those comorbid patients.

ANTIBODY-INDUCED REJECTION OF PIG PROISLET XENOGRAFTS IN CD4+ T CELL-DEPLETED DIABETIC MICE

1990 ◽  
Vol 50 (4) ◽  
pp. 657-662 ◽  
Author(s):  
CHARMAINE J. SIMEONOVIC ◽  
J. DENNIS WILSON ◽  
RHODRI CEREDIG
Keyword(s):  
T Cell ◽  
Cd4 T Cell ◽  
Diabetic Mice

CD4+ T cell effectors can become memory cells with high efficiency and without further division

10.1038/90643 ◽  
2001 ◽  
Vol 2 (8) ◽  
pp. 705-710 ◽  
Author(s):  
Hui Hu ◽  
Gail Huston ◽  
Debra Duso ◽  
Nancy Lepak ◽  
Eulogia Roman ◽  
...  
Keyword(s):  
T Cell ◽  
High Efficiency ◽  
Cd4 T Cell ◽  
Memory Cells

scholarly journals CD4 T–cell memory can persist in the absence of class II

2000 ◽  
Vol 355 (1395) ◽  
pp. 407-411 ◽  
Author(s):  
Susan L. Swain
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Specific Antigen ◽  
Class Ii ◽  
Cd4 T Cell ◽  
T Cell Memory ◽  
Memory Cells ◽  
Short Period ◽  
Memory Cd4 T Cells

To understand how memory CD4 T cells are generated we have re–examined the requirements for continuing antigen stimulation in the generation and persistence of this population. We find that specific antigen is only required for a short period during the activation of naive CD4 Tcells and is not required for memory generation from activated CD4 T cells or for persistence of resting memory cells generated by transfer of activated CD4 to adoptive hosts. Moreover, transfer of activated CD4 T cells to class–II–deficient hosts, indicates that T cR–class II major histocompatibility interaction is also unnecessary for either the transition from activated CD4 T cell to resting memory cells or for persistence over an eightweek period. Thus the signals regulating generation and maintenance of memory are fundamentally different from those which regulate the expansion of effector CD4 T–cell populations which include antigen itself and the CD4 T–cell autocrine cytokines induced by antigen.

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