CD137-CD137L Interactions Regulate B-cell Autoimmunity during Alloimmune Responses.
Jong Soo Lee1,3, Hong Rae cho2,3, Byungsuk Kwon3,4, Kyung Sun Park1,3, Juyang Kim3,4, Hyejung Kim3,4, Sangjoon Park2,3.
1Internal Medicine, Ulsan University Hospital, College of Medicine, Ulsan, Korea; 2Surgery, Ulsan University Hospital, College of Medicine, Ulsan, Korea; 3Biomedical Research Center, Ulsan University Hospital, College of Medicine, Ulsan, Korea; 4School of Bilogical Sciences, University of Ulsan, Ulsan, Korea
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.
