Preferential infiltration of interleukin‐4‐producing CXCR 4 + T cells in the lesional muscle but not skin of patients with dermatomyositis

Summary Dermatomyositis ( DM ) and polymyositis ( PM ) are collectively termed autoimmune myopathy. To investigate the difference between muscle‐ and skin‐infiltrating T cells and to address their role for myopathy, we characterized T cells that were directly expanded from the tissues. Enrolled into this study were 25 patients with DM and three patients with PM . Muscle and skin biopsied specimens were immersed in c RPMI medium supplemented with interleukin ( IL) ‐2 and anti‐ CD 3/ CD 28 antibody‐conjugated microbeads. The expanded cells were subjected to flow cytometry to examine their phenotypes. We analysed the cytokine concentration in the culture supernatants from the expanded T cells and the frequencies of cytokine‐bearing cells by intracellular staining. There was non‐biased in‐vitro expansion of tissue‐infiltrating CD 4 + and CD 8 + T cells from the muscle and skin specimens. The majority of expanded T cells were chemokine receptor ( CCR) type 7 – CD 45 RO + effecter memory cells with various T cell receptor ( TCR) V βs. The skin‐derived but not muscle‐derived T cells expressed cutaneous lymphocyte antigen ( CLA) and CCR 10 and secreted large amounts of IL ‐17 A , suggesting that T helper type 17 ( T h17) cells may have a crucial role in the development of skin lesions. Notably, the frequency of IL ‐4‐producing chemokine (C‐X‐C motif) receptor (CX CR) 4 + T h2 cells was significantly higher in the muscle‐derived cells and correlated inversely with the serum creatine phosphokinase (CPK) and lactate dehydrogenase ( LDH) levels. stromal‐derived factor (SDF) ‐1/ CXCL 12, a ligand for CXCR 4, was expressed at a high level in the vascular endothelial cells between muscular fasciculi. Our study suggests that T cell populations in the muscle and skin are different, and the T h2 cell infiltrate in the muscle is associated with the low severity of myositis in DM .