Journal
INTERNATIONAL IMMUNOLOGY
Volume 18, Issue 6, Pages 827-835Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxl019
Keywords
apoptosis; CTL; cytokine; T cell activation; T cell differentiation
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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.
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