Regulatory role of peritoneal NK1.1(+) alpha beta T cells in IL-12 production during Salmonella infection

NK1.1(+)alpha beta T cells emerge in the peritoneal cavity after an i.p. in fection with Salmonella choleraesuis in mice. To elucidate the role of the NK1.1(+)alpha beta T cells during murine salmonellosis, mice lacking NK1.1( +)alpha beta T cells by disruption of TCR beta (TCR beta(-/-)), p,m (beta(2 )m(-/-)), or J alpha 281 (J alpha 281(-/-)) gene were i.p, inoculated with S, choleraesuis. The peritoneal exudate T cells in wild type (wt) mice on d ay 3 after infection produced IL-4 upon TCR alpha beta stimulation, whereas those in TCR beta(-/-), beta(2)m(-/-), or J alpha 281(-/-) mice showed no IL-4 production upon the stimulation, indicating that NK1.1(+)alpha beta T cells are the main source of IL-4 production at the early phase of Salmonel la infection. Neutralization of endogenous IL-4 by administration of anti-I L-4 mAb to wt mice reduced the number of Salmonella accompanied by increase d IL-12 production by macrophages after Salmonella infection. The IL-12 pro duction by the peritoneal macrophages was significantly augmented in mice l acking NK1.1(+)alpha beta T cells after Salmonella infection accompanied by increased serum IFN-gamma level. The aberrantly increased IL-12 production in infected TCR beta(-/-) or J alpha 281(-/-) mice was suppressed by adopt ive transfer of T cells containing NK1.1(+)alpha beta T cells but not by th e transfer of T cells depleted of NK1.1(+)alpha beta T cells or T cells fro m J alpha 281(-/-) mice. Taken together, it is suggested that NK1.1(+)alpha beta T cells eliciting IL-4 have a regulatory function in the IL-12 produc tion by macrophages at the early phase of Salmonella infection.