Predominant Appearance of NK1.1⁺ T Cells Producing IL-4 May Be Involved in the Increased Susceptibility of Mice with the Beige Mutation during Salmonella Infection

C57BL/6 mice with the beige mutation (beige mice) showed a high susceptibility to infection with Salmonella choleraesuis compared with C57BL/6 (B6) control mice, as assessed by bacterial number in the peritoneal cavity and the liver. The appearance of NK1.1⁺CD3^- NK cells was significantly suppressed, while NK1.1⁺ T cells were increased in the peritoneal cavity of beige mice after Salmonella infection. The expression level of IL-4 mRNA was much higher in freshly isolated NK1.1⁺ T cells of the infected beige mice, but the expression level of IFN-γ mRNA was lower than that in the infected control mice. The NK1.1⁺ T cells produced more IL-4 in response to TCRαβ cross-linking, whereas IFN-γ production upon TCR triggering was significantly impaired in the beige mice compared to that in the control mice. Furthermore, the generation of Salmonella-specific Th1 cells producing IFN-γ was significantly inhibited in the peritoneal cavity of beige mice after Salmonella infection. However, administration of anti-IL-4 neutralizing mAb to beige mice during salmonellosis restored the generation of Salmonella-specific Th1 cells and decreased the susceptibility to Salmonella. These results suggested that the predominant activation of NK1.1⁺ T cells producing IL-4 over those producing IFN-γ may be at least partly involved in the poor generation of Salmonella-specific protective Th1 cells, resulting in the increased susceptibility of beige mice to Salmonella infection.