The endothelial junction adhesion molecule CD146 appears on activated lymphocytes in vitro and in very low percentages of circulating lymphocytes in healthy individuals. Preliminary evidence suggests that CD146 facilitates adherence of these cells to the endothelium, and perhaps transendothelial migration. 24 synovial fluids (SF) were obtained from 21 patients with various arthritic conditions. Peripheral blood (PB) was obtained from 6 of these patients and PB from 23 healthy individuals. Our data indicate CD4+CD146+ cells accumulate in SFs preferentially compared to PB and these cells display a unique genotypic profile from their CD146- counterparts. Using Affymetrix HG-U133+ PM arrays, comparative data analysis between CD146 positive and negative SF CD4+ cells revealed differential expression of 230 probesets. CD146+ CD4+ cells compared to CD146- CD4+ cells displayed increased expression of numerous genes including collagen type VI, alpha 3, CXCL13, and CD109 and decreased expression CCR7 and cytotoxicity-associated genes such as granzymes h and k, perforin, and CCL5. Both CD109 and CXCL13 have been shown to mediate T cell - B cell interactions and the upregulation of these genes on CD146+ T cells in SF may indicate these cells facilitate such interactions.