Regulatory role of peritoneal NK1.1⁺αβ T cells in IL-12 production during Salmonella infection

NK1.1⁺αβ T cells emerge in the peritoneal cavity after an i.p. infection with Salmonella choleraesuis in mice. To elucidate the role of the NK1.1⁺αβ T cells during murine salmonellosis, mice lacking NK1.1⁺αβ T cells by disruption of TCRβ (TCRβ(-/-)), β₂m (β₂m(-/-)), or Jα281 (Jα281(-/-)) gene were i.p. inoculated with S. choleraesuis. The peritoneal exudate T cells in wild type (wt) mice on day 3 after infection produced IL- 4 upon TCRαβ stimulation, whereas those in TCRα(-/-), β₂m(-/-), or Jα281(-/-) mice showed no IL-4 production upon the stimulation, indicating that NK1.1⁺αβ T cells are the main source of IL-4 production at the early phase of Salmonella infection. Neutralization of endogenous IL-4 by administration of anti-IL-4 mAb to wt mice reduced the number of Salmonella accompanied by increased IL-12 production by macrophages after Salmonella infection. The IL-12 production by the peritoneal macrophages was significantly augmented in mice lacking NK1.1⁺αβ T cells after Salmonella infection accompanied by increased serum IFN-γ level. The aberrantly increased IL-12 production in infected TCRβ(-/-) or Jα281(-/-) mice was suppressed by adoptive transfer of T cells containing NK1.1⁺αβ T cells but not by the transfer of T cells depleted of NK1.1⁺αβ T cells or T cells from Jα281(-/-) mice. Taken together, it is suggested that NK1.1⁺β T cells eliciting IL-4 have a regulatory function in the IL-12 production by macrophages at the early phase of Salmonella infection.