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The role of the innate immune response in Th1 cell development following Leishmania major infection
Author(s) -
SchartonKersten Tanya,
Scott Phillip
Publication year - 1995
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 - 10.1002/jlb.57.4.515
Subject(s) - biology , immunology , immune system , cd8 , interleukin 12 , t cell , interleukin 15 , innate immune system , cell , interferon , interleukin 21 , natural killer cell , interleukin , cytokine , cytotoxic t cell , in vitro , biochemistry , genetics
Infection of mice with the protozoan parasite Leishmania major is an established model with which to study the in vivo development of CD4 + Th cell subsets. Interferon‐γ (IFN‐γ), produced by natural killer (NK) cells (AsGM1 + , CD4 ‐ , CD8 ‐ , CD3 ‐ ), regulates CD4 + T cell subset development and early resistance to L. major. Rapid Th1 cell development and resistance to infection occur in mice that develop an NK cell response early after infection (C3H and immunized BALB/c mice), whereas mice that lack an early NK cell response demonstrate delayed Thl cell development and enhanced early disease (C57BL/6) or lack detectable Thl cell development al together and develop a progressive, fatal infection (BALB/c). Analysis of the requirements for NK cell acti vation in C3H mice revealed that the NK cell response is both interleukin‐2 (IL‐2) and IL‐12 dependent. Although delayed IL‐12 production in C57BL/6 mice precludes NK cell activation, the eventual development of a Thl re sponse appears to be IL‐12 dependent. In contrast, con comitant production of inhibitory factors (IL‐4, IL‐10, and transforming growth factor β ) with IL‐12 and IL‐2 prevents NK cell activation in BALB/c mice. Together, these observations support a paradigm of in vivo Th1 cell development that involves IL‐12‐depcndcnt stimulation of IFN‐γ production by NK cells. J. Lcukoc. Biol. 57: 515–522; 1995.