Preferential expression of alphaEbeta7 integrin (CD103) on CD8+ T cells in the psoriatic epidermis: regulation by interleukins 4 and 12 and transforming growth factor-beta

Abstract

Background: Intraepidermal T lymphocytes are a critical element for sustaining the lesional pathology of psoriasis. Integrin alphaEbeta7 (CD103), a ligand for E-cadherin, may play a role in the localization of pathogenic T cells within the epidermis of psoriatic lesions. However, little information is available regarding alphaEbeta7 expression on intraepidermal T cells in psoriasis.

Objectives: To examine alphaEbeta7 expression on intraepidermal T cells in psoriatic lesions and the regulation of alphaEbeta7 expression on T cells in response to cytokines.

Methods: T-cell expression of alphaEbeta7 was examined by immunohistochemistry and flow cytometry. In vitro regulation of alphaEbeta7 expression on CD4+ or CD8+ T cells purified from peripheral blood of healthy donors was also examined.

Results: Immunohistochemical staining revealed expression of alphaEbeta7 on a greater proportion of epidermal T cells than dermal T cells. Nearly 30% of intraepidermal CD4+ T cells were found to express alphaEbeta7 on flow cytometry, whereas more than 80% of intraepidermal CD8+ T cells expressed this integrin. In contrast, few T cells expressed alphaEbeta7 in the peripheral blood of psoriatic patients. The in vitro culture experiment confirmed that alphaEbeta7 was preferentially expressed on CD8+ T cells after stimulation with anti-CD3 monoclonal antibodies. Addition of transforming growth factor-beta and interleukin-4 upregulated alphaEbeta7 expression on T cells, whereas interleukin 12 downregulated this. Furthermore, alphaEbeta7 expression on established memory CD8+ T cells was not so reversible as that on CD4+ T cells.

Conclusions: Preferential and stable expression of alphaEbeta7 on CD8+ T cells may be involved in the lesional pathology of psoriasis.