Submitted April 14, 2008
Accepted February 5, 2009
Regulatory T cells modulate differentially the maturation and apoptosis of human CD8-T cell subsets
Maria Nikolova, Jean-Daniel Lelievre, Matthieu Carriere, Armand Bensussan, and Yves Levy*
INSERM, Unite U955, Creteil, France
Universite Paris 12, Faculte de Medecine, Creteil, France
AP-HP, Groupe Henri-Mondor Albert-Chenevier, Immunologie clinique, Creteil, France
* Corresponding author; email: yves.levy{at}hmn.aphp.fr.
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 regulatory CD4+ CD25high T cells (Treg) as a key factor for the inefficiency of CD8+ T cell responses in viral persistence. Little is known about the effects of Treg on the homeostasis of healthy donor CD8+ T cells. The present study demonstrates that Treg exert differential effects on CD8+ T cell subsets. Treg inhibited mostly the polyclonal proliferation of CD27- effector cells when compared to CD27+ memory CD8+ T cells. Moreover, they inhibited the polyclonal and antigen-driven differentiation of memory cells into functional effectors as defined by IFN-
secretion and induction of CD160 expression. Finally, Treg reduced the apoptosis of memory, and 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 PD-1, on CD8+ T cells after activation. Thus, in the settings of a healthy immune system, Treg fine-tune the memory/effector cell balance and promote the accumulation of long-living memory cells in case of strong stimulation.
