BACTERIALLY PREEXPOSED T-CELLS IMPAIR BACTERIAL ELIMINATION BY NON-TH1 TH2 CELL MECHANISMS IN A MODEL OF INTRAABDOMINAL INFECTION/

Background. Escherichia coli preexposure in mice results in impaired e limination of subsequent intra-abdominal infections by a CD4+ T cell-d ependent process. Certain gram-negative infections have been shown to induce T-helper-(Th)2-type CD4+ T-cell differentiation, which correlat es with impaired elimination of infection and death. We hypothesized t hat E coli preexposure impairs subsequent bacterial elimination as a c onsequence of Th2 differentiation and that interleukin-12 (IL-12) trea tment could reverse this differentiation and minimize the effects off coli preexposure. Methods. After preexposure to E coli or other specie s, BALB/c mice or interferon-gamma (IFN-gamma)-deficient mice, treated with or without IL-12, were given a standard intra-abdominal infectio n (E coli, Bacteroides fragilis, and adjuvant). Cohorts were killed fo r abscess quantification, in vitro T-cell proliferative responsiveness , and cytokine secretory profiles. Splenic lymphocytes preexposed in v ivo to other types of bacteria were transferred to naive mice before i ntra-abdominal infection to determine whether preexposure, eliciting t he lymphocyte-dependent response, was species specific. Results. E col i preexposure alone caused no Th1 or Th2 shift; increased the prolifer ative responses of T cells; and, in combination with IL-12 therapy, ca used markedly decreased IL-2 and IL-4 responses and an increased IFN-g amma response. IL-12 therapy did not change the response to intra-abdo minal infection despite its ability to cause marked Th1 polarization. IFN-gamma-deficient mice responded to E coli preexposure no differentl y than did wild-type mice. Transfer of lymphocytes preexposed to Pseud omonas aeruginosa, Klebsiella pneumoniae, and hemolytic E coli but not other types of nosocomial pathogens caused the development of more ab scesses just as transfer off coli preexposed lymphocytes had. Conclusi ons. CD4+ T cells responsive to E coli preexposure regulate subsequent intra-abdominal abscess formation by a mechanism not explained by the Th1/Th2 paradigm. Preexposure to hemolytic E coli and other Enterobac teriaceae alters responses to intra-abdominal infection.