Roles of NKT cells in resistance against infection with Toxoplasma gondii and in expression of heat shock protein 65 in the host macrophages.

Abstract We investigated the roles of γδ T, NK, and NK1.1 + T-like (NKT) cells in protective immunity against infection with Toxoplasma gondii . γδ T cells, NKT and NK cells, and NK cells in BALB/c mice were depleted by treatment with anti-TCR-γδ monoclonal antibody (mAb), anti-interleukin-2 receptor beta chain (IL-2Rβ) mAb, and anti-asialoGM1 Ab, respectively, and these mice were infected with T. gondii . Treatment of mice with anti-TCR-γδ mAb aggravated toxoplasmosis, while treatment with anti-asialoGM1 Ab had no effects. Treatment with anti-IL-2Rβ mAb enhanced the expression of heat shock protein 65 (HSP65) and gamma interferon (IFN-γ) mRNA, while it inhibited interleukin-4 (IL-4) mRNA expression, ameliorating toxoplasmosis. In addition to NK cells, anti-IL-2Rβ mAb eliminated cells expressing IL-2Rβ and intermediate levels of CD3 (IL-2Rβ + CD3 int ). Mice treated with anti-IL-2Rβ mAb decreased the number of DX5 + CD3 int cells, which are considered to be equivalent to NK1.1 + T cells in NK1.1 allele-negative strains. IL-2Rβ + CD3 int cells isolated from splenic and hepatic lymphoid cells were confirmed to express the TCR-Vα14 transcript. The magnitude of HSP65 induction in macrophages correlated with the protective potential against T. gondii infection after treatment with the antibodies, supporting our previous finding that γδ T cells play an essential role in the induction of HSP65 in host macrophages. Interestingly, NKT cells suppressed the expression of γδ T cell-induced HSP65 and IFN-γ. Furthermore, depletion of IL-2Rβ + CD3 int cells suppressed the IL-4 mRNA expression. These results suggest that NKT cells may be the cells responsible for suppression of protective immunity against T. gondii infection by interfering with the γδ T cell-induced HSP65 expression, possibly through the generation of IL-4.