T Lymphocyte Responses to Antigens of Gram-Negative Bacteria in Pyelonephritis

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We showed previously that large numbers of T lymphocytes accumulate within a few days in the kidneys of rats with ascending pyelonephritis induced with Escherichia coli or Pseudomonas aeruginosa. CD4 + T cells propagated from the lesions exhibited MHC-restricted proliferative responses to formalin-fixed bacteria of the species used to induce infection. In the present study we investigated further the nature of the antigens responsible for the T cell proliferation and studied the ability of different bacterial strains and species to produce proliferative responses. We found that heatkilled bacteria were more stimulatory than formalin-fixed bacteria, and that soluble supernatants of heat-killed organism were also effective. The stimulatory effects of supernatants were destroyed by trypsin and the responses were MHC-restricted. Twelve different E. coli strains, with or without characteristics of uropathogenicity in humans, were all highly stimulatory to T cells derived from a kidney infected with a single E. coli strain. Strains of Klebsiella pneumoniae, Enterobacter aerogenes, and Serratia marcescens—species of Enterobacteriaceae closely related to E. coli —were also stimulatory, whereas more distantly related bacteria— Proteus, Morganella, and P. aeruginosa—were not. T cells propagated from kidneys infected with P. aeruginosa responded to supernatants of this organism, but not to E. coli supernatants. We conclude that a protein antigen (or antigens) shared by strains of E. coli and related Enterobacteriaceae, but not by other gram-negative bacteria, produce MHC-restricted proliferative responses of CD4 + T cells that infiltrate rat kidneys infected with E. coli.