CD137-CD137L Interactions Regulate B-cell Autoimmunity during Alloimmune Responses

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Transfer of H2-Abbm12 to CD57BL/6 mice breaks B-cell autoimmunity which results in chronic graft-versus-host disease (GVHD) with a SLE-like phenotype. In this disease model, CD137-/- recipients were shown to be severely impaired in autoantibody production but instead had an acute type of GVHD, indicating that Th1 responses were activated in CD137-/- mice. Analysis of CD137-/- spleens demonstrated that there was an increase in IL-12-producing CD8α+ DCs, which was caused by the absence of CD137L signaling in pre-DCs. Accordingly, IFN-γ –producing donor Th1 cells were preferentially differentiated in CD137-/- spleens, providing an explanation for why chronic GVHD was converted toward acute GVHD in CD137-/- recipients. Interestingly, differentiation of follicular helper T cells was severely impaired in CD137-/- spleens and so was that of germinal center B cells and plasma cells. Taken together, our results suggest that CD137-CD137L interactions regulate many aspects of immune cell differentiation during alloimmune responses.

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