Current perspectives on the role of CD8+ T cells in systemic sclerosis

Despite long-standing recognition of the importance of T cells in systemic sclerosis (SSc; scleroderma), the role of CD8+ T cells in disease pathogenesis has not been well studied. Our work has shown that over-production of the pro-fibrotic cytokine IL-13 by peripheral blood effector/memory CD8+ T cells is critical for predisposing patients to more severe forms of cutaneous fibrosis. Moreover, IL-13-producing CD8+ T cells induce a pro-fibrotic phenotype in normal and SSc dermal fibroblasts, and exhibit a strong cytotoxic activity ex vivo. We also found that CD8+ T cells are predominantly abundant in the skin lesions of patients in the early stages of diffuse cutaneous (dc)SSc compare to late-stage disease patients. Isolation of CD8+ T cells from the lesional skin of early active dcSSc patients, established that they are skin-resident, express cytolytic molecules and co-express extremely high levels of IL-13 and IFNγ. Other recent studies corroborate these findings and together strongly suggest that CD8+ T cells contribute to SSc pathogenesis through the production of high levels of cytokines with pro-inflammatory and pro-fibrotic function as well as by exhibiting a cytotoxic activity.