Regulatory T cells differentially modulate the maturation and apoptosis of human CD8+ T-cell subsets
- 7 May 2009
- journal article
- Published by American Society of Hematology in Blood
- Vol. 113 (19), 4556-4565
- https://doi.org/10.1182/blood-2008-04-151407
Abstract
The balanced manifestation of effector functions and the generation of long-living memory cells is a hallmark of efficient CD8+ T-cell response. Accumulating data pinpoint CD4+ CD25high regulatory T (Treg) cells as a key factor for the inefficiency of CD8+ T-cell responses in viral persistence. Little is known about the effects of Treg cells on the homeostasis of healthy donor CD8+ T cells. The present study demonstrates that Treg cells exert differential effects on CD8+ T-cell subsets. Treg cells inhibited mostly the polyclonal proliferation of CD27− effector cells compared with CD27+ memory CD8+ T cells. Moreover, they inhibited the polyclonal and antigen-driven differentiation of memory cells into functional effectors as defined by IFN-γ secretion and induction of CD160 expression. Finally, Treg cells reduced the apoptosis of memory but not of effector and terminal effector cell populations. These effects were at least in part mediated by a decreased expression of PD-L1, but not of programmed death 1 (PD-1), on CD8+ T cells after activation. Thus, in the setting of a healthy immune system, Treg cells fine-tune the memory/effector cell balance and promote the accumulation of long-living memory cells in case of strong stimulation.This publication has 56 references indexed in Scilit:
- PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infectionThe Journal of Experimental Medicine, 2006
- Agonist Anti-GITR Antibody Enhances Vaccine-Induced CD8+ T-Cell Responses and Tumor ImmunityCancer Research, 2006
- Premature Induction of an Immunosuppressive Regulatory T Cell Response during Acute Simian Immunodeficiency Virus InfectionThe Journal of Infectious Diseases, 2006
- Association ofCTLA4 polymorphism with regulatory T cell frequencyEuropean Journal of Immunology, 2005
- Memory CD8 T-Cell Differentiation during Viral InfectionJournal of Virology, 2004
- Human CD4+CD25+ regulatory cells have marked and sustained effects on CD8+ T cell activationEuropean Journal of Immunology, 2003
- CD4+CD25+ T Cells Regulate Virus-specific Primary and Memory CD8+ T Cell ResponsesThe Journal of Experimental Medicine, 2003
- Lineage relationship and protective immunity of memory CD8 T cell subsetsNature Immunology, 2003
- Phenotypic and Functional Separation of Memory and Effector Human CD8+ T CellsThe Journal of Experimental Medicine, 1997
- Immunological Memory and Protective Immunity: Understanding Their RelationScience, 1996