DIFFERENTIAL REGULATION OF THE INTERLEUKIN-12 RECEPTOR DURING THE INNATE IMMUNE-RESPONSE TO LEISHMANIA-MAJOR

Previous studies have shown the central role of interleukin 12 (IL-12) in the development of resistance to Leishmania major infection in C3H mice. We now show that during the innate immune response the lymph no de cells of L. major-infected C3H mice upregulate the IL-12 receptor o n CD4(+), CD8(+), and B220(+) cells. An increase in the ability of the lymph node cells to bind IL-12 correlates with 9.3- and 4.6-fold incr eases in the mRNA expression levels of the IL-12R beta 1 and -beta 2 s ubunits, respectively. In contrast, BALB/c mice, which are susceptible to L. major infection, have no increase in the ability of the lymph n ode cells to bind IL-12 and correspondingly smaller increases in the m RNA expression levels of the IL-12R beta 1 and -beta 2 subunits of 2- and 1.5-fold, respectively, Neutralizing IL-4 and the administration o f exogenous IL-12 upregulate IL-12R expression in BALB/c mice, while t he neutralization of IL-12 in C3H mice blocks increased IL-12 receptor expression. These experiments reveal an important role for the regula tion of the IL-12 receptor during the innate immune response after inf ection of mice with a pathogen.