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Differential effects of IL‐12 on the generation of alloreactive CTL mediated by murine and human dendritic cells: a critical role for nitric oxide
Author(s) -
Nishioka Yasuhiko,
Wen Hua,
Mitani Kayo,
Robbins Paul D.,
Lotze Michael T.,
Sone Saburo,
Tahara Hideaki
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0402205
Subject(s) - mixed lymphocyte reaction , ctl* , biology , immunology , interferon gamma , nitric oxide , immune system , dendritic cell , t lymphocyte , interleukin 4 , cytotoxic t cell , microbiology and biotechnology , in vitro , t cell , biochemistry , cd8 , endocrinology
We examined the mechanisms involved in interleukin (IL)‐12‐mediated suppression of cellular immunity in mice using allogeneic mixed leukocyte reaction (MLR) stimulated by dendritic cells (DCs) in vitro and compared the effect of IL‐12 on MLR in mice and humans. Although IL‐12 stimulated human MLR, the addition of IL‐12 or interferon‐γ (IFN‐γ) resulted in a dose‐dependent suppression of MLR in mice. The treatment with N G ‐monomethyl‐ l ‐arginine (L‐NMMA) completely abrogated IL‐12‐ and IFN‐γ‐mediated suppression of MLR in mice. Furthermore, IL‐12 enhanced the alloreactive cytolytic T lymphocyte (CTL) induction in human MLR, whereas the addition of L‐NMMA was required to generate alloreactive CTLs in the presence of IL‐12 in mice. Nitric oxide (NO) was detected only in mouse MLR. Murine DCs could produce NO, but neither human CD34 + cell‐ nor monocyte‐derived DCs produced a detectable amount of NO. These results suggest that NO produced by DCs might play an important role in IL‐12‐mediated immune suppression in mice but not in humans.