Administration of Superantigens Protects Mice from LethalListeria monocytogenesInfection by Enhancing Cytotoxic T Cells

Abstract

Superantigens stimulate T-cell-receptor Vβ-selective T-cell proliferation accompanying the release of cytokines, which may eventually protect the host from microbial infections. We investigated here whether superantigens can rescue the host from lethal bacterial infection. Mice were pretreated withStaphylococcus aureusenterotoxin B (SEB) 1 and 2 days before bacterial infection, and the mortality of infected mice was assessed. SEB pretreatment protected mice from lethal infection withListeria monocytogenesbut not from lethal infection withStreptococcus pyogenes. This enhanced protection was also observed upon pretreatment with recombinant streptococcal pyrogenic exotoxin A. Furthermore,L. monocytogenes-specific delayed-type hypersensitivity (DTH) due to type 1 helper T (Th1) cells and the cytotoxicity of CD8⁺T cells were significantly enhanced after SEB administration and bacterial infection. Depletion of either CD4⁺T cells or CD8⁺T cells in SEB-pretreated mice completely abolished this protection. This phenomenon was ascribed to the elimination ofL. monocytogenes-specific CD8⁺cytotoxic T lymphocytes (CTL). It was found that CD4⁺T cells contributed to the induction of the CTL populations. Furthermore, SEB pretreatment of heat-killedL. monocytogenes-immunized mice enhanced the protection from challenge ofL. monocytogenes. Taken together, these results indicated that administrations of superantigens protected mice from infection withL. monocytogenes, which was dependent on the enhancedL. monocytogenes-specific CTL activity in the presence of CD4⁺T cells, and superantigens exhibited adjuvant activity in the immunization against intracellular pathogens.