engleski

Increased perforin expression in peripheral blood lymphocytes in psoriatic patients in exacerbation phase of disease

Psoriasis is T cell mediated autoimmune skin disease characterized by infiltration of inflammatory cells, especially T lymphocytes and production of inflammatory cytokines, mostly of Th1 type. Oscillations in phenotype of T lymphocytes are observed in peripheral blood (PB) and skin lesions, depending on stage of disease. CD4+ T cell predominance in exacerbated psoriatic plaques and CD8+ T cells in resolutive lesions are demonstrated. Cell mediated cytotoxicity reactions (CMC) are reactions mediated by secretion of cytolytic molecule perforin and granzyme or binding of FasL (CD95L) with Fas receptor (CD95) on target cell. CD8+ T lymphocytes and to a certain degree CD4+ T lymphocytes as well as NK cells mediate in CMC. Perforin (P) is cytolytic molecule expressed in the granules of cytolytic cells both CTL and NK cells, released in the contact with the target cells subsequently exerting either necrotic or apoptotic (in collaborations with serine esterases) cell death. The role of cytolytic pathway mediated by perforin is recognized in psoriasis in PBL and in lesions but still insufficiently defined. The aim of our new investigation was to analyze expression of perforin in the PBL of psoriatic patients during the exacerbation and remission phase of disease and elucidate a role of perforin mediated cytotoxicity in fluctuating nature of disease. Psoriatic patients in exacerbation and remission phase of chronic psoriasis and healthy persons, age and sex matched to psoriatic group, were investigated. Peripheral blood lymphocytes (PBL) were tested either by single or double staining, for simultaneous detection of P (intracellular antigen) and cell surface antigens by cell permeabilization method and flow cytometric analyses. Single staining analyses showed a marked increase of total P+ cells, as well as CD3+, CD8+ and CD56+ lymphocytes in PBL in exacerbation phase compared to remission. The results obtained by double staining reveal a significantly higher percentage of CD8+P+ cells in the exacerbation phase of disease, as well as CD56+P+ cells resembling NK cells. Average fluorescence intensity (AFI) for P+ cells showed a significantly higher quantity of perforin among CD4+P+ cells in the exacerbation phase compared to remission. These results point on the potential role of cytolytic mechanisms mediated by perforin in exacerbation phase of disease compared to remission.

perforin; peripheral blood lymphocytes; psoriase

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