P04 Circulating CD8 T cells from patients with psoriasis are functionally impaired

Abstract Introduction and aims Psoriasis is an immune-mediated inflammatory disease affecting the skin, with T cells playing a pivotal role in its pathogenesis. However, the phenotypic and functional characteristics of CD8 T cells in peripheral blood and their contribution to psoriasis progression remain poorly understood. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from 7 individuals with mild-to-moderate psoriasis and 10 healthy controls. Cells were activated in vitro via two distinct pathways: T-cell receptor (TCR)-independent stimulation, utilizing phorbol 12-myristate 13-acetate and ionomycin for 6 h, and TCR-dependent stimulation, employing anti-CD3/CD28 antibodies for 24 h. Subsequently, the phenotypic and functional features of CD8 T cells were analysed by flow cytometry. Results Individuals with psoriasis showed a decreased frequency of circulating CD8 memory T cells (P = 0.019), particularly those displaying a CC chemokine receptor (CCR7)-effector phenotype (P = 0.02), when compared with healthy participants. Moreover, although CD8 T-cell subsets showed comparable levels of the skin-homing marker CCR4, they displayed a notable increase in coinhibitory receptor B- and T-lymphocyte attenuator expression relative to healthy individuals (P = 0.002). Following cell activation, anti-CD3/CD28-stimulated CD8 T-cell subsets exhibited markedly decreased expression of CD69 (P < 0.001), interferon γ (P < 0.001) and granzyme B (P < 0.001). Finally, patients with psoriasis showed a substantial decrease in the frequency of activated CD27+ CD8 T cells following anti-CD3/CD28 activation when compared with healthy individuals (P = 0.0002). Conclusions A significant reduction in circulating CD8 T memory cells and a decreased release of mediators from CD8 T cells were observed in individuals with mild-to-moderate psoriasis. This observation suggests that peripheral CD8 T function is impaired in psoriasis, which could be explained by CD8 T cells being in the skin trafficked out of peripheral circulation.