Peripheral blood mononuclear cells (PBMCs) obtained from atopic dermatitis (AD) patients produced low levels of IFN-gamma in response to Dermatophagoides farinae antigen (Der f Ag) plus IL-2 or OKT3 MoAb in contrast with PBMCs obtained from healthy donors. The reduced IFN-gamma production in AD patients' T cells appeared to be derived from the defect of CD4+ T cells but not CD8+ T cells. Indeed, from the cytoplasmic staining analysis of cytokines, it was demonstrated that the frequency of IFN-gamma producing CD4+ T cells (TH1 cells) in AD patients was markedly lower than that of healthy donors. From the phenotypic analysis using flow cytometry, it was also found that the number of CD4+ CD45RO+ memory type T cells was significantly reduced in AD patients compared with that of healthy donors. In addition to quantitative defect of memory type CD4+ T cells, functional defect of CD4+ CD45RO+ memory type T cells was also demonstrated in AD patients. Enriched CD4+ CD45RO+ T cells obtained from AD patients, who exhibited greatly reduced delayed-type hypersensitivity (DTH) response in tuberculin test, showed no significant TH1 immunity in terms of IFN-gamma production by stimulation with OKT3 MoAb or purified protein derivative (PPD). Thus, the immunological abnormality of TH1 immunity in AD patients appeared to be induced in concomitant with both the quantitative and qualitative defect of memory type CD4+ T cells.

To determine the therapeutic mechanism of PUVA in psoriasis vulgaris, the effects of PUVA on activated T lymphocytes were investigated in vitro. Peripheral blood mononuclear cells (PBMC) obtained from healthy volunteers were activated with Con A stimulation (Con A blasts). Both untreated PBMC and Con A blasts were irradiated with UVA light in the presence of 8-methoxypsoralen (8-MOP). The expressions of CD4, CD8, VLA-4 and LFA-1 of PBMC and Con A blasts were stained with each monoclonal antibody and the intensity of fluorescence was analyzed by FACScan. PUVA-treated PBMC showed decreased response to both Con A and PHA stimulation. PUVA treatment also suppressed the IL-2 production of Con A blasts and IL-2 response of PBMC with increasing UVA fluence. The expressions of LFA-1, VLA-4, CD4, CD8 and CD25 (IL-2R) molecules were decreased in PUVA-treated Con A blasts. Con A blasts were more sensitive than untreated PBMC to PUVA treatment. These results suggest that the therapeutic effects of PUVA on psoriasis vulgaris can be induced by suppression of the expression of cell surface molecules of activated T lymphocytes.

No abstract

No abstract

No abstract