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.

Characterization of dermal dendritic cells in psoriasis. Autostimulation of T lymphocytes and induction of Th1 type cytokines.

“…While in both circumstances PP skin-derived DDCs and blood-derived DDCs did stimulate autologous T cell proliferation (confirming the existence of circulating autoreactive T cells) (5)(6)(7)18), the skin -derived DDCs were always capable of greater T cell stimulation compared with blood-derived DDCs using the same individual T cells as responders. Thus, these results suggest that PP skin-derived DDCs may also bear T cell mitogenic signals beyond HLA-DR and B7.…”

IL-10 is a key cytokine in psoriasis. Proof of principle by IL-10 therapy: a new therapeutic approach.

“…It is well established that psoriasis is a T cell-dependent immune disease (2,5,6,(8)(9)(10)21). The pathophysiological process is probably initiated by presentation of so far unknown "psoriasis-related antigens" by specialized cutaneous APCs (46,47).…”

A Global Gene Expression Analysis of the Peripheral Blood Mononuclear Cells Reveals the Gene Expression Signature in Psoriasis

“…Although the precise etiology is largely unknown, it is strongly believed that psoriasis is caused by the combination of multiple factors, including the genetic background and environmental insults. Until the introduction of cyclosporine A (CsA) as a treatment modality, psoriasis had primarily been regarded as a skin disease related with epidermal keratinocytes [4][5][6] .…”