Rapid development of a gamma interferon-secreting glycolipid/CD1d-specific Valpha14+ NK1.1- T-cell subset after bacterial infection.

The phenotypic and functional changes of glycolipid presented by CD1d(glycolipid/CD1d) specific Valpha14+ T cells in the liver of mice at early stages of bacterial infection were investigated. After Listeria monocytogenes infection or interleukin-12 (IL-12) treatment, alpha-galactosylceramide/CD1d tetramer-reactive (alpha-GalCer/CD1d+) T cells coexpressing natural killer (NK) 1.1 marker became undetectable and, concomitantly, cells lacking NK1.1 emerged in both euthymic and thymectomized animals. Depletion of the NK1.1+ subpopulation prevented the emergence of alpha-GalCer/CD1d+ NK1.1- T cells. Before infection, NK1.1+, rather than NK1.1-, alpha-GalCer/CD1d+ T cells coexpressing CD4 were responsible for IL-4 production, whereas gamma interferon (IFN-gamma) was produced by cells regardless of NK1.1 or CD4 expression. After infection, IL-4-secreting cells became undetectable among alpha-GalCer/CD1d+ T cells, but considerable numbers of IFN-gamma-secreting cells were found among NK1.1-, but not NK1.1+, cells lacking CD4. Thus, NK1.1 surface expression and functional activities of Valpha14+ T cells underwent dramatic changes at early stages of listeriosis, and these alterations progressed in a thymus-independent manner. In mutant mice lacking all alpha-GalCer/CD1d+ T cells listeriosis was ameliorated, suggesting that the subtle contribution of the NK1.1- T-cell subset to antibacterial protection is covered by more profound detrimental effects of the NK1.1+ T-cell subset.