While on the one hand BiP 336–355 induced PBMC proliferation and correlated with clinical arthritis activity and with the levels of circulating anti- BiP/citrullinated BiP antibodies, continuous oral administration of BiP 456–475 to mice with CIA resulted in improvement of joint inflammation and histologic scores, reduction of CD4+ T cell proliferation, increased numbers of CD4+CD25+FoxP3+ regulatory T cells and CD4+FoxP3+ T cells, and increased secretion of IL-10 from T cells. Here, CD4 is linked to arthritic joint disease.