Immune Responses in Resistant and Susceptible Strains of CD4-Mutant Mice Infected with Leishmania major

Abstract

We examined the immune response of CD4-mutant mice that have soluble form of CD4 in the circulation without expression of CD4 on T cell surface. We infected the CD4-mutant mice of BALB/c and C57BL/6 backgrounds with Leishmania major and subsequently examined parameters of disease and immune response. In contrast to wild-type (wt) BALB/c mice, mutant mice of both strains showed decreased parasite replication and an intense leishmanial antigen-specific delayed-type hypersensitivity (DTH) response. In vitro cytokine analysis revealed that popliteal lymph node cells (LNC) from mutant mice of both strains secreted little or no detectable interleukin-4 (IL-4) and they secreted interferon-γ (IFN-γ) at levels similar to those of wt mice. The cytokine profile shows that a lack of IL-4 production underlies the lack of T helper type 2 (Th2) response. As validation of the impaired Th2 response, infection of the mice with Nippostrongylus brasiliensis, a typical Th2 inducer, showed a lack of Th2 response. Furthermore, in contrast to LNC from wt mice, Th2 cells were not induced from naive LNC of mutant mice when the cells were cultured in the presence of IL-4 and anti-IL-12 antibody. These findings indicate that the lack of IL-4 production is due to a lack of CD4 on T cells and that IFN-γ production is independent of CD4 on T cells. Thus, Th1 and Th2 responses to leishmanial infection are not due to the balance of IL-4/IFN-γ that are produced, but the production of IL-4 determines whether a Th1 or Th2 response will develop.