Proliferation capacity and cytotoxic activity are mediated by functionally and phenotypically distinct virus-specific CD8 T cells defined by interleukin-7R{alpha} (CD127) and perforin expression.

Détails

ID Serval
serval:BIB_241EC3C720DF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Proliferation capacity and cytotoxic activity are mediated by functionally and phenotypically distinct virus-specific CD8 T cells defined by interleukin-7R{alpha} (CD127) and perforin expression.
Périodique
Journal of Virology
Auteur⸱e⸱s
Cellerai C., Perreau M., Rozot V., Enders F.B., Pantaleo G., Harari A.
ISSN
1098-5514[electronic], 0022-538X[linking]
Statut éditorial
Publié
Date de publication
2010
Volume
84
Numéro
8
Pages
3868-3878
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Résumé
Cytotoxicity and proliferation capacity are key functions of antiviral CD8 T cells. In the present study, we investigated a series of markers to define these functions in virus-specific CD8 T cells. We provide evidence that there is a lack of coexpression of perforin and CD127 in human CD8 T cells. CD127 expression on virus-specific CD8 T cells correlated positively with proliferation capacity and negatively with perforin expression and cytotoxicity. Influenza virus-, cytomegalovirus-, and Epstein-Barr virus/human immunodeficiency virus type 1-specific CD8 T cells were predominantly composed of CD127(+) perforin(-)/CD127(-) perforin(+), and CD127(-)/perforin(-) CD8 T cells, respectively. CD127(-)/perforin(-) and CD127(-)/perforin(+) cells expressed significantly more PD-1 and CD57, respectively. Consistently, intracellular cytokine (gamma interferon, tumor necrosis factor alpha, and interleukin-2 [IL-2]) responses combined to perforin detection confirmed that virus-specific CD8 T cells were mostly composed of either perforin(+)/IL-2(-) or perforin(-)/IL-2(+) cells. In addition, perforin expression and IL-2 secretion were negatively correlated in virus-specific CD8 T cells (P < 0.01). As previously shown for perforin, changes in antigen exposure modulated also CD127 expression. Based on the above results, proliferating (CD127(+)/IL-2-secreting) and cytotoxic (perforin(+)) CD8 T cells were contained within phenotypically distinct T-cell populations at different stages of activation or differentiation and showed different levels of exhaustion and senescence. Furthermore, the composition of proliferating and cytotoxic CD8 T cells for a given antiviral CD8 T-cell population appeared to be influenced by antigen exposure. These results advance our understanding of the relationship between cytotoxicity, proliferation capacity, the levels of senescence and exhaustion, and antigen exposure of antiviral memory CD8 T cells.
Mots-clé
CD8-Positive T-Lymphocytes/immunology, Cell Degranulation, Cell Proliferation, Cells, Cultured, Cytotoxicity, Immunologic, Flow Cytometry, Humans, Interferon-gamma/biosynthesis, Interleukin-2/biosynthesis, Interleukin-7 Receptor alpha Subunit/biosynthesis, Perforin/biosynthesis, T-Lymphocyte Subsets/immunology, Tumor Necrosis Factor-alpha/biosynthesis, Virus Diseases/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/04/2010 10:17
Dernière modification de la notice
20/08/2019 13:02
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