CD4 and rheumatoid arthritis: In addition to altered cytokine milieu in peripheral blood, constitutive STAT3 phosphorylation in RA may involve aberrations in the expression or activation of intracellular kinases or negative regulators upstream of STAT3 or in transcriptional activity of STAT3. In this context it is of note that elevated levels of STAT3 mRNA in circulating monocytes and CD3+ T cells [33] and downregulation of suppressor of cytokine signaling 3 (a negative STAT3 pathway regulator) in CD4+ T cells [41] have been reported in RA patients.