asialo-gm1-ganglioside and Toxoplasmosis

We investigated the roles of gamma delta T, NK, and NK1.1(+) T-like (NKT) cells in protective immunity against infection with Toxoplasma gondii. gamma delta T cells, NKT and NK cells, and NK cells in BALB/c mice were depleted by treatment with anti-TCR-gamma delta monoclonal antibody (mAb), anti-interleukin-2 receptor beta chain (IL-2R beta) mAb, and anti-asialoGM1 Ab, respectively, and these mice were infected with T. gondii. Treatment of mice with anti-TCR-gamma delta mAb aggravated toxoplasmosis, while treatment with anti-asialoGM1 Ab had no effects. Treatment with anti-IL-2R beta mAb enhanced the expression of heat shock protein 65 (HSP65) and gamma interferon (IFN-gamma) mRNA, while it inhibited interleukin-4 (IL-4) mRNA expression, ameliorating toxoplasmosis. In addition to NK cells, anti-IL-2R beta mAb eliminated cells expressing IL-2R beta and intermediate levels of CD3 (IL-2R beta(+) CD3(int)). Mice treated with anti-IL-2R beta 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-2R beta(+) CD3(int) cells isolated from splenic and hepatic lymphoid cells were confirmed to express the TCR-V alpha 14 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 gamma delta T cells play an essential role in the induction of HSP65 in host macrophages. Interestingly, NKT cells suppressed the expression of gamma delta T cell-induced HSP65 and IFN-gamma. Furthermore, depletion of IL-2R beta(+) 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 gamma delta T cell-induced HSP65 expression, possibly through the generation of IL-4.

Topics: Animals; Antibodies; Bacterial Proteins; Chaperonin 60; Chaperonins; Female; G(M1) Ganglioside; Immunity, Innate; Interferon-gamma; Killer Cells, Natural; Macrophages; Mice; Mice, Inbred BALB C; Receptors, Antigen, T-Cell, gamma-delta; Receptors, Interleukin-2; T-Lymphocytes; Toxoplasma; Toxoplasmosis

The intraperitoneal infection with Toxoplasma gondii (T. gondii) caused accumulation of gamma delta T, NK, NK1.1+T-like (NKT) cells at inflamed sites. To clarify the roles of these cells in protection against T. gondii at the inflamed sites, BALB/c mice were depleted of gamma delta T, NK, NK and NKT cells by treatment with antibody against TCR-gamma delta, asialoGM1 or Interleukin-2 receptor beta-chain (IL-2 R beta), respectively, prior to infection. Mice treated with anti-TCR-gamma delta monoclonal antibody (mAb) became more susceptible to infection, whereas mice treated with anti-IL-2R beta mAb acquired resistance. Treatment with anti-asialoGM1 Ab showed no effect. We previously reported that heat shock protein 65 (HSP65) in macrophages induced by gamma delta T cells plays an essential role in protective immunity against T. gondii infection, by preventing apoptotic death of infected macrophages. In the present study, we showed that treatment with anti-IL-2R beta mAb, but not with anti-asialoGM1 Ab, enhanced the HSP65 induction in macrophages, and inhibited Interleukin-4 (IL-4) expression in nonadherent peritoneal exudate cells. Furthermore, neutralization of endogenous IL-4 by anti-IL-4 mAb enhanced the HSP65 induction in macrophages. These findings suggest that NKT cells, but not NK cells, negatively regulate the protective immunity against T. gondii infection possibly by producing IL-4 and suppressing HSP65 induction.

Topics: Animals; Antibody Specificity; Bacterial Proteins; Chaperonin 60; Chaperonins; Female; G(M1) Ganglioside; Gene Expression; Immunity, Innate; Interferon-gamma; Interleukin-4; Killer Cells, Natural; Lymphocyte Depletion; Macrophages, Peritoneal; Mice; Mice, Inbred BALB C; Neutralization Tests; Peritoneal Cavity; Receptors, Antigen, T-Cell, gamma-delta; Receptors, Interleukin-2; RNA, Messenger; T-Lymphocytes; Toxoplasma; Toxoplasmosis