In this review we have highlighted the pluripotent effects of anti-CD137-mediated costimulation with emphasis on T-dependent B cell function in normal and autoimmune prone mice. We have shown that anti-CD137 treatment of normal mice during antigen priming, but not thereafter, suppresses the induction of T-dependent humoral immunity as well as CD8 T cell immunity. We suggest that the mechanism through which this occurs may involve CD137-mediated signaling in dendritic cells and other CD137-expressing APC. In studying lupus prone mice, contrary to our observations in normal mice, we find that we can suppress established T-dependent humoral autoimmune responses. On the other hand, as in normal mice, we fail to suppress established T-dependent humoral immunity to conventional antigens in NZB/W F1 mice, and we speculate how this may occur. We have also included some of our unpublished studies on the regulatory function of B cells and their suppression of anti-tumor immunity. These data, while tangential to the main thrust of this review, highlight how B cell may mediate suppression of anti-tumor immunity and how anti-CD137 treatment can override suppression. Finally, we show that repeated treatment of normal mice with anti-CD137 mAbs has a dramatic T cell-dependent effect on lymphocyte trafficking, homeostasis, hematopoiesis and liver pathology. Many questions remain to be answered concerning the mechanisms that drive these events, and it is important to understand how dysregulation of immune cell homeostasis relates to the positive effects of anti-CD137 treatment of autoimmune disease and cancer.
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