Work

Abatacept Reduces CD319 + ( SLAMF7 ) Cytotoxic T Cells and Cytokine Production in Systemic Sclerosis

Year: 2026

Type: article

Abstract: OBJECTIVE: Systemic sclerosis (SSc) is characterized by immune dysregulation and fibrosis. We investigated whether abatacept modulates CD319/SLAMF7-expressing cytotoxic T cells implicated in diffuse cutaneous SSc. METHODS: In this ancillary ASSET trial analysis, peripheral blood mononuclear cells from 67 participants were analyzed at baseline and months one, three, and six. Flow cytometry quantified CD4+CD319+ and CD8+CD319+ T cells, cytotoxic and activation markers, and stimulated intracellular interleukin-4 (IL-4), IL-17A, and interferon-γ (IFN-γ). Analyses compared abatacept-treated molecular endotypes with placebo and related immune changes to modified Rodnan skin score (mRSS) change. Skin single-cell RNA sequencing included five healthy controls and eight patients with SSc. RESULTS: At baseline, CD319+ T cells showed greater cytokine production, activation, and granzyme and perforin expression than CD319- T cells in 60 evaluable participants (P < 0.001 to P < 0.0001). Abatacept reduced CD4+CD319+ and CD8+CD319+ T cell frequencies at month six; placebo did not. Effects were strongest in patients in the fibroproliferative group, in whom CD8+CD319+ T cells decreased versus placebo (n = 7 versus n = 36; P = 0.0377). In this endotype, abatacept reduced IL-4 in CD4+CD319+ and CD8+CD319+ T cells at month three (P = 0.0468 and P = 0.0287) and IL-17A in CD8+CD319+ T cells at month six (P = 0.0004), whereas IFN-γ was unchanged. Reduction in CD4+CD319+ T cells correlated with mRSS improvement in abatacept-treated patients (r = 0.5297, P = 0.0423). Skin single-cell RNA sequencing showed increased SLAMF7 expression in SSc T cells (P = 0.017), enriched within cytotoxic subsets. CONCLUSION: CD319+ T cells represent highly differentiated, activated cytotoxic effector populations in SSc. Abatacept selectively modulates these cells and suppresses associated profibrotic and proinflammatory cytokines, particularly in the fibroproliferative subtype, in which CD319+ T cell reductions correlate with clinical improvement.

Source: Arthritis & Rheumatology

DOI: 10.1002/art.70301