Although CD137 activation upon ligation with CD137L provokes bidirectional signalling which induces proliferation and differentiation of both T and B cells, knocking out CD137 paradoxically induces more autoantibody production, higher level of pathogenic CD4+ and double negative T cells (CD3+CD4-CD8-B220+), more severe cutaneous lupus, glomerulonephritis, and death in the MRL/lpr mouse model [63]. This evidence concerns the gene CD4 and glomerulonephritis.