Although the precise pathophysiology of RA remains to be determined, it is widely appreciated that CD4+ T helper (Th) cells play a pivotal role in the pathogenesis of RA; this is supported by accumulating evidence, for example, MHC class II haplotype human leukocyte antigen (HLA)-DRB1 was identified as the strongest disease susceptibility gene and a high efficacy of cytotoxic T lymphocyte antigen 4 (CTLA4)-Ig blocking T cell co-stimulatory molecules for the treatment of RA15–17. This evidence concerns the gene CD4 and rheumatoid arthritis.