CD40L in autoimmunity and mucosally induced tolerance
J. Clin. Invest. Mi-Na Kweon, et al. 109:171 doi:10.1172/JCI14930 [
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Figure 1Models for the effects on mucosally induced tolerance of perturbing the CD40L-CD40 interaction. (
a) In the untreated wild-type mouse, CD40 on dendritic cells (DCs) and other APCs interacts with CD40L expressed on T cells of several subsets, including CD4 and CD8 cells, as well as a CD25 CD4 population of regulatory T cells (Tr). This interaction can lead to both active, antigen-specific CTL responses and the suppression of Th function and inflammation. The latter effects appear to be implicated in mucosally induced tolerance to dietary antigens and endogenous bacteria. (
b) As shown by Hänninen et al. in this issue of the
JCI (
8), transient treatment with mAb anti-CD40L can prevent induction of CTLs, while apparently leaving some of the other responses intact. Thus, mucosally induced tolerance is not compromised by this treatment. (
c) In case of the permanent blockage of CD40L-CD40, as occurs in
CD40L–/– mice, the additional loss of some immunosuppressive signaling cascade and/or of a population of Tr cells prevents mucosally induced tolerance.