In addition, CTLA-4 Ig alleviated disease activity in the absence of CD4+ T cells in a CIA model6, and a number of approaches targeting T cells, including anti-CD4 antibody7, have shown no clear benefits in clinical trials of RA patients, suggesting that the action of CTLA-4 Ig may not depend solely on the T cell costimulatory pathway. Here, CD4 is linked to rheumatoid arthritis.