IL-4 influences the differentiation and the susceptibility to activation-induced cell death of human naive CD8+ T cells.
It is now well established that the cytokine environment influences the activation, differentiation, proliferation and death of T lymphocytes during the primary response to antigen. Using an in vitro model, we investigated the influence of IL-4, added at the onset of TCR stimulation, on phenotypic and functional markers of naive CD8+ T cell activation including the up-regulation of activation markers, proliferation as well as the susceptibility to activation-induced cell death (AICD). We report that IL-4, unlike IL-2 added at the onset of repeated TCR stimulation of naive CD8+ T cells prevents AICD, in part due to its ability to maintain the level of the survival-related protein Bcl-2. Moreover, TCR-triggered activation of naive CD8+ T cells in the presence of IL-4 leads to the development of a CD8+ T cell subset that proliferates normally, but which fails to exhibit characteristic activation parameters such as the up-regulation of CD25 and Granzyme B. Taken together, these results demonstrate that exposure to IL-4 during primary activation influences CD8+ T cell differentiation by inducing the development of a sub-population of AICD-resistant, proliferation-competent cells that do not show some of the typical features of CD8+ T cell activation.
Riou
Catherine
C
Laboratoire d'Immunologie, Centre de recherche du CHUM, Pavillon Edouard-Asselin, Hôpital Saint-Luc, 264 René-Lévesque Boulevard E, Montréal, Québec H2X 1P1, Canada.
Dumont
Alain R
AR
Yassine-Diab
Bader
B
Haddad
Elias K
EK
Sekaly
Rafick-Pierre
RP
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D019254:Genes, bcl-2 / Q000276:immunology; D053804:Granzymes; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases