Th1 is the predominant helper T cell subset that produces GM-CSF in the joint of rheumatoid arthritis

Granulocyte macrophage colony-stimulating factor (GM-CSF), an immunomodulatory cytokine, is an emerging therapeutic target of rheumatoid arthritis (RA).1 Although GM-CSF is produced by various types of cells, including synovial fibroblasts, the importance of GM-CSF-producing CD4 T cells in the pathogenesis of RA was reported.2 Moreover, GM-CSF has been shown to be the critical effector cytokine produced by interleukin (IL)-23-stimulated Th17 cells in mice, leading to the prevailing notion that GM-CSF is a Th17-related cytokine.3 However, in humans, a distinct subset of CD4 T cells that produce only GM-CSF has recently been identified.4 The ‘GM-CSF-only’ T cells are characterised by the lack of lineage defining cytokines (interferon (IFN)-γ, IL-17 and IL-4) and are regulated independently of the master transcriptional regulators, T-bet, RORγt or GATA3. Furthermore, in contrast to mice, GM-CSF production by human CD4 T cells was promoted in Th1 conditions and was also detected in Th1 cells. At present, it is unclear which helper CD4 T cell subsets produce GM-CSF in human RA joints. Therefore, in this study, we performed multicolour flow cytometric analysis of cytokine production in CD4 T cells from patients with RA. Lymphocytes in the peripheral blood (PB) and in joints from the same patients were analysed to compare the profiles of cytokine production. Synovial fluid (SF) samples were obtained from seven patients by arthrocentesis, while synovial membrane (SM) samples were obtained from seven other patients who underwent joint replacement surgery. The mean age and disease duration of the patients was 63.5±15.5 and 16.5±10.1 years, respectively. Twelve patients (86%) were positive for RF and/or anti-CCP2 antibody, and the mean C reactive protein level was 1.2±1.1 mg/dL. In total, 11 (79%), 10 (71%) and 4 (29%) patients received …