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With(out) a little help from my friends: an IL-12/CD40L-mediated feed-forward loop between CD8+ T cells and DCs
Martijn A Nolte1, Rene A W van Lier
1Adaptive Immunity Lab, Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory AMC/UvA, Amsterdam, The Netherlands. m.nolte@sanquin.nl
Insights
CD40-CD40L interactions are crucial for T and B cell development. Interestingly, CD8(+) T cells can express CD40L, forming a self-sustaining loop that impacts effector CD8(+) T-cell formation.
Area of Science:
- Immunology
- Cellular immunology
- T-cell biology
Background:
- CD40-CD40L interactions regulate B-cell differentiation and T-cell formation.
- CD40L is typically expressed on activated CD4(+) T cells, aiding B cells and dendritic cells (DCs).
- CD8(+) T cells can also express CD40L, challenging existing models.
Purpose of the Study:
- To investigate the role of CD40L expression on CD8(+) T cells.
- To explore the mechanisms regulating CD40L expression in CD8(+) T cells.
- To understand the implications for effector CD8(+) T-cell development.
Main Methods:
- Analysis of CD40L expression on CD8(+) T cells.
- Investigating the induction of CD40L by IL-12 and T-cell receptor (TCR) signaling.
- Studying the impact on effector CD8(+) T-cell responses.
Main Results:
- CD8(+) T cells express CD40L.
- CD40L expression on CD8(+) T cells is induced by IL-12 and TCR signaling.
- This forms a self-sustaining feed-forward loop for CD40L expression.
Conclusions:
- CD8(+) T cells expressing CD40L contribute to their own development.
- This finding shifts the paradigm of CD4(+) T-cell help in CD8(+) T-cell responses.
- Highlights a novel self-sustaining mechanism in T-cell immunity.
Abstract:
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.
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