Decreased Expression Of IFN-γ Research Articles

UVB Irradiation of Normal Human Skin Favors the Development of Type-2 T-cells In Vivo and in Primary Dermal Cell Cultures¶

To determine the effect of UVB exposure on the balance of type-1 or type-2 T-cells in skin, we examined the expression of key markers interferon (IFN)-γ and interleukin (IL)-4 in cryostat sections. IFN-γ mRNA was clearly detectable in nonirradiated control skin, and IFN-γ protein was found in 2% of the dermal CD3pos T-cells, whereas IL-4 mRNA was hardly detectable, and no IL-4 protein was found. In contrast, IL-4 mRNA expression increased upon irradiation, and IL-4 was found in 2% of the T-cells at day 2 after UVB-exposure. Concomitantly, IFN-γ mRNA expression decreased, and IFN-γ protein became absent. We also analyzed T-cells present in primary dermal cell cultures, which were used as an in vitro equivalent of the in vivo situation. As compared with T-cells from control skin, T-cells in dermal cell cultures from UVB-exposed skin displayed an increased IL-4 and decreased IFN-γ expression. No such skewing occurred when the T-cells from irradiated skin were cloned in the absence of a dermal microenvironment. Except for an occasional positive T-cell, type-1–associated cell-surface markers (CCR5, CXCR3) or type-2 markers (CCR3, CD30, CRTH2) were undetectable in situ. But these markers were expressed on cultured dermal T-cells from UVB-exposed and control skin at a comparable level, but did not correlate with the IFN-γ and IL-4 production. Altogether, UVB-induced changes of the dermal microenvironment favor the development of type-2 T-cells.

Flow cytometric analysis of IL-4, IL-13 and IFN-γ expression in peripheral blood mononuclear cells and detection of circulating IL-13 in patients with atopic dermatitis provide evidence for the involvement of type 2 cytokines in the disease

Recent studies have shown increased T-helper (Th) 2 cytokine expression and decreased IFN-gamma expression in peripheral blood from patients with atopic dermatitis (AD). In the present study, we examined the cytokine expression in peripheral blood mononuclear cells in patients with AD and tested how the cytokine profile correlated with the patients' age, severity and laboratory findings. Peripheral blood mononuclear cells obtained from 20 patients with AD were stimulated with phorbol 12-myristate 13-acetate and ionomycin, and were examined for the frequencies of CD4+ cells expressing IL-4, IL-13 and IFN-gamma at the single cell level using intracellular cytokine staining and flow cytometry. There was a significant positive correlation between IL-4 and IL-13 expression in CD4+ cells. Expression levels of both IL-4 and IL-13 in CD4+ cells were significantly correlated with peripheral blood eosinophilia. These findings suggest that CD4+ cells producing IL-4 and IL-13 play important roles in the pathogenesis of AD. IFN-gamma expression did not correlate with either IL-4 or IL-13 expression, or with blood eosinophilia. We also measured serum levels of IL-13 in 144 patients with AD using enzyme-linked immunosorbent assay, and found 16 patients with detectable levels of serum IL-13. IL-13+ patients had significantly higher serum IgE levels than IL-13- patients, suggesting a direct association between serum levels of IL-13 and IgE. It was also shown that the IL-13+ group was significantly younger in age than the IL-13- group, although the implication of this finding is not clear at present. The sum of these findings suggested that the predominance of Th2 cells and the consequent overexpression of IL-4 and IL-13 in peripheral blood may be deeply involved in the pathogenetic process of AD.

Variation of Cytokine Patterns Related to Therapeutic Response in Diffuse Cutaneous Leishmaniasis

Diffuse cutaneous leishmaniasis is a rare entity characterized by disseminated cutaneous nodules associated with specific anergy to leishmanial antigens. A low but not absent IFN-gamma expression by cells present in cutaneous lesions has been documented during the active phase of diffuse cutaneous leishmaniasis. In this study we confirm this observation, and extend it by showing a similar pattern in peripheral blood mononuclear cells and the variation of mRNA cytokine expression pattern during different stages of the disease. During active disease, patients did not express mRNA for IFN-gamma, while expressing mRNA for IL-2, IL-4, and IL-10. In contrast, an expression of IFN-gamma and low IL-10 was observed after treatment-induced transient healing of cutaneous lesions. In three patients we have been able to analyze a third PBMC sample obtained after clinical relapse, documenting in all of them decreased IFN-gamma expression with no expression of IL-10. Although there was an association between the appearance of IFN-gamma expression and clinical improvement, with marked expression of IFN-gamma mRNA and decreased expression of mRNA for IL-10 after treatment, this was not sufficient to prevent relapse in these patients. Therefore, it is possible that factors other than the cytokines characteristic of the Th1 and Th2 balance are implicated in the inability of diffuse cutaneous leishmaniasis patients to mount an anti-Leishmania immune response causing clinical improvement.