Accessory signaling by CD40 for T cell activation: induction of Th1 and Th2 cytokines and synergy with interleukin-12 for interferon-γ production
✍ Scribed by Xiaohui Peng; Ahmad Kasran; Petra A. M. Warmerdam; Mark De Boer; Jan L. Ceuppens
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 738 KB
- Volume
- 26
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Accessory signaling by CD40 for T cell activation: induction of Thl and Th2 cytokines and synergy with interleukin42 for interferon-y production
The interaction of CD40 ligand (CD4OL) on activated T cells with CD40 on B cells, monocytes and dendritic cells is essential for humoral immunity and for up-regulation of antigen-presenting cell (APC) functions, as a result of signaling through CD40. There are also some indications that after interaction with CD40, CD40L can directly signal T cells. In this study we demonstrate that upon stimulation of human peripheral blood T cells through the T cell receptor (TCR)/CD3 complex, CD40/CD40L interaction strongly enhances the production of Thl cytokines such as interleukin (1L)-2 and interferon (1FN)-y and Th2 cytokines such as IL-4, IL-5 and IL-10 by a direct effect on T cells. Furthermore, CD40/ CD40L interaction synergizes with IL-12 in selectively enhancing IFN-y production by purified anti-CD3-stimulated T cells. These effects were observed at both the protein and the mRNA level. Both CD4' and CDS' T cells were able to produce IFN-y in the presence of helper signals from IL-12 and CD40, although CDS' T cells were less active. Since CD40/CD40L interaction also upregulates IL-12 production and B7 expression by APC, our results suggest that CD40/CD40L interaction is bidirectional, and promotes activation of both APC and T cells.