With(out) a little help from my friends: An IL‐12/CD40L‐mediated feed‐forward loop between CD8+ T cells and DCs

CD40–CD40L interactions are important for both antigen‐dependent B‐cell differentiation and effector and memory T‐cell formation. The prevailing view is that CD40L is expressed on activated CD4⁺ T cells, which enables them to provide help to high‐affinity B cells in GCs and to license DCs for efficient induction of CD8⁺ T‐cell responses. Interestingly, CD8⁺ T cells themselves can also express CD40L and, in this issue of the European Journal of Immunology, Thiel and colleagues [Eur. J. Immunol. 2013. 43: 1511‐1517] show that CD40L expression on these cells can be part of a self‐sustaining feed‐forward loop, in which expression of CD40L is induced by IL‐12 and TCR signaling. This provides a paradigm shift in our thinking about the requirements of effector CD8⁺ T‐cell development and the role herein of CD4⁺ T cells to provide help in this process.