Differential expressions of heme oxygenase-1 gene in CD25- and CD25+ subsets of human CD4+ T cells.

Growing evidence suggests that the immunomodulatory heme oxygenase-1 (HO-1) may have an important role in regulating T-cell responses. In this study, we investigated whether CD4(+)CD25(-) and CD4(+)CD25(+) T cells of human CD4(+) subpopulation could differentially express HO-1. Our results obtained from qualitative reverse transcriptase-polymerase chain reaction and quantitative flow cytometry analyses revealed that the CD4(+)CD25(+) T cells constitutively express HO-1 and that T cell stimulation with plate-bound anti-CD3 in combination with soluble anti-CD28 not only induced HO-1 gene expression in the CD4(+)CD25(-) T cells but also up-regulated HO-1 gene expression in the CD4(+)CD25(+) T cells. Our further studies showed that CD28 signal alone was enough to induce HO-1 expression and CD3 signal, of which signal alone did not induce HO-1 expression, was required at least for full HO-1 expression in both CD25(-) and CD25(+) subsets of human CD4(+) T cells. In addition, transfection of human Jurkat T cells with HO-1 suppressed the cellular proliferation, and this effect was reversed by zinc protoporphyrin, a specific HO competitive inhibitor. Taken together, we have first reported that human CD4(+)CD25(+) regulatory T cells constitutively express HO-1 and that HO-1 inhibits Jurkat T cell proliferation.