Heme oxygenase 1 expression by human CD4(+) T cells is not sufficient for their development of immunoregulatory capacity

作者：Biburger Markus; Theiner Gabi; Schaedle Mirjam; Schuler Gerold; Tiegs Gisa^*

来源：Journal of Leukocyte Biology, 2010, 87(2): 192-201.

DOI：10.1189/jlb.0508280

• tolerance
• regulatory T cells
• immune modulation
• CD4(+)CD25(+) T-regs
• proliferation

HO-1 is the only inducible one of three isoenzymes that catalyzes the oxidative degradation of heme. HO-1 is inducible by various cellular stress factors and exerts cytoprotective and immunomodulatory effects. Recent publications demonstrated that HO-1 is constitutively expressed by CD4(+)CD25(+) T-regs and induced in CD4(+)CD25(-) T cells upon FoxP3 transfection. Here, we investigated whether HO-1 was essential and sufficient for human T-regs to exert immunosuppression in vitro. PGJ(2) induced pronounced expression of HO-1 in CD4(+)CD25(-) T cells without accompanying FoxP3 induction. Treatment of CD4(+)CD25(-) T cells with PGJ(2) decreased their proliferation, whereas the HO-1 inhibitor SnPP enhanced the proliferation of HO-1-expressing T-regs, suggesting that HO-1 may modulate the proliferative capacity of T lymphocytes. HO-1 modulation by SnPP treatment of T-regs or PGJ(2) treatment of CD4(+)CD25(-) T cells neither suppressed nor induced immune-modulatory function in these cells, respectively, as measured by responder-cell proliferation and/or IL-2 production. In summary, these data suggest that HO-1 expression by T-regs might contribute to their typical reluctance to proliferate but does not account independently for their suppressive functions. J. Leukoc. Biol. 87: 193-202; 2010.

• 出版日期2010-2