Genomic, phenotypic, and functional analyses of T cells in patients with psoriasis undergoing systemic cyclosporin A treatment

Abstract

Recent studies have demonstrated that cyclosporin A (CyA) exerts a beneficial effect on psoriasis. It remains unclear, however, whether T-cell immune responses are definitely impaired in psoriasis and whether the anti-psoriatic effect of CyA is mediated by interference with T-cell activation. To study these questions, 20 patients with severe psoriasis were treated with oral CyA (5 mg/kg/d) for 12 weeks and examined for several phenotypic and functional properties of peripheral blood T cells before and after therapy. The analyses included CD3, CD4, and CD8 phenotypes, IL-2 production and IL-2 receptor expression following Con A stimulation, proliferative responses to PHA, and in vivo responsiveness to a foreign antigen, PPD. When the values of patients before therapy and healthy individuals were compared, no statistically significant differences were detected in any of these analyses. Furthermore, none of these T-cell properties were changed after 12 weeks of treatment. To assess possible minor mutations in T-cell-related genes in psoriasis, the T-cell receptor beta-chain locus was analyzed by Southern hybridization. With a cDNA probe for C beta 1, a polymorphic fragment of congruent to 9 kb was detected in Eco RI digests in one of 20 patients and in four of 10 healthy individuals examined. No polymorphism was detected in Bam HI digests in any individual. These results fail to support the hypothesis that a general or "systemic" alteration in T-cell immunity plays a central role in the pathogenesis of psoriasis and in the action of CyA against this skin disorder.