Relationship of CD 146 expression to secretion of interleukin (IL)‐17, IL‐22 and interferon‐γ by CD 4 + T cells in patients with inflammatory arthritis

Summary Expression of the adhesion molecule, CD146/MCAM/MelCAM, on T cells has been associated with recent activation, memory subsets and T helper type 17 ( T h17) effector function, and is elevated in inflammatory arthritis. T h17 cells have been implicated in the pathogenesis of rheumatoid arthritis ( RA ) and spondyloarthritides ( SpA ). Here, we compared the expression of CD 146 on CD 4 + T cells between healthy donors ( HD ) and patients with RA and SpA [ankylosing spondylitis ( AS ) or psoriatic arthritis ( PsA )] and examined correlations with surface markers and cytokine secretion. Peripheral blood mononuclear cells ( PBMC ) were obtained from patients and controls, and synovial fluid mononuclear cells ( SFMC ) from patients. Cytokine production [elicited by phorbol myristate acetate ( PMA )/ionomycin] and surface phenotypes were evaluated by flow cytometry. CD 146 + CD 4 + and interleukin ( IL )‐17 + CD 4 + T cell frequencies were increased in PBMC of PsA patients, compared with HD , and in SFMC compared with PBMC . CD 146 + CD 4 + T cells were enriched for secretion of IL ‐17 [alone or with IL ‐22 or interferon ( IFN )‐γ] and for some putative T h17‐associated surface markers ( CD 161 and CCR 6), but not others ( CD 26 and IL‐ 23 receptor). CD 4 + T cells producing IL ‐22 or IFN ‐γ without IL ‐17 were also present in the CD 146 + subset, although their enrichment was less marked. Moreover, a majority of cells secreting these cytokines lacked CD 146. Thus, CD 146 is not a sensitive or specific marker of T h17 cells, but rather correlates with heterogeneous cytokine secretion by subsets of CD 4 + helper T cells.