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Blood, 7 May 2009, Vol. 113, No. 19, pp. 4556-4565. Prepublished online as a Blood First Edition Paper on February 25, 2009; DOI 10.1182/blood-2008-04-151407. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-04-151407v1 113/19/4556    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Nikolova, M. Articles by Lévy, Y. Search for Related Content PubMed PubMed Citation Articles by Nikolova, M. Articles by Lévy, Y. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Regulatory T cells differentially modulate the maturation and apoptosis of human CD8+ T-cell subsets Maria Nikolova1,2,*, Jean-Daniel Lelievre1,3,4,*, Matthieu Carriere1, Armand Bensussan1, and Yves Lévy1,3,4 1 Inserm U955, Creteil, France; 2 National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria; 3 Université Paris 12, Faculté de Medecine, Creteil, France; and 4 Assistance Publique–Hôpitaux de Paris (AP-HP), Groupe Henri-Mondor Albert-Chenevier, Immunologie Clinique, Creteil, France 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- 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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