TY - JOUR
T1 - Bacterially preexposed T cells impair bacterial elimination by non- Th1/Th2 cell mechanisms in a model of intra-abdominal infection
AU - Gleason, T. G.
AU - Sawyer, R. G.
AU - Pruett, T. L.
AU - Bankey, P. E.
AU - Lederer, J. A.
AU - Alverdy, J.
PY - 1998
Y1 - 1998
N2 - Background. Escherichia coli preexposure in mice results in impaired elimination of subsequent intra-abdominal infections by a CD4+ T cell- dependent process. Certain gram-negative infections have been shown to induce T-helper-(Th)2-type CD4+ T-cell differentiation, which correlates with impaired elimination of infection and death. We hypothesized that E coli preexposure impairs subsequent bacterial elimination as a consequence of Th2 differentiation and that interleukin-12 (IL-12) treatment could reverse this differentiation and minimize the effects of E coli preexposure. Methods. After preexposure to E coli or other species, BALB/c mice or interferon-T (IFN-γ)-deficient mice, treated with or without IL-12, were given a standard intra-abdominal infection (E coli, Bacteroides fragilis, and adjuvant). Cohorts were killed for abscess quantification, in vitro T-cell proliferative responsiveness, and cytokine secretory profiles. Splenic lymphocytes preexposed in vivo to other types of bacteria were transferred to naive mice before intra-abdominal infection to determine whether preexposure, eliciting the lymphocyte-dependent response, was species specific. Results. E coli preexposure alone caused no Th1 or Th2 shift; increased the proliferative responses of T cells; and, in combination with IL-12 therapy, caused markedly decreased IL-2 and IL-4 responses and an increased IFN-γ response. IL-12 therapy did not change the response to intra-abdominal infection despite its ability to cause marked Th1 polarization. IFN-γ-deficient mice responded to E coli preexposure no differently than did wild-type mice. Transfer of lymphocytes preexposed to Pseudomonas aeruginosa, Klebsiella pneumoniae, and hemolytic E coli but not other types of nosocomial pathogens caused the development of more abscesses just as transfer of E coli preexposed lymphocytes had. Conclusions. 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 Enterobacteriaceae alters responses to intra-abdominal infection.
AB - Background. Escherichia coli preexposure in mice results in impaired elimination of subsequent intra-abdominal infections by a CD4+ T cell- dependent process. Certain gram-negative infections have been shown to induce T-helper-(Th)2-type CD4+ T-cell differentiation, which correlates with impaired elimination of infection and death. We hypothesized that E coli preexposure impairs subsequent bacterial elimination as a consequence of Th2 differentiation and that interleukin-12 (IL-12) treatment could reverse this differentiation and minimize the effects of E coli preexposure. Methods. After preexposure to E coli or other species, BALB/c mice or interferon-T (IFN-γ)-deficient mice, treated with or without IL-12, were given a standard intra-abdominal infection (E coli, Bacteroides fragilis, and adjuvant). Cohorts were killed for abscess quantification, in vitro T-cell proliferative responsiveness, and cytokine secretory profiles. Splenic lymphocytes preexposed in vivo to other types of bacteria were transferred to naive mice before intra-abdominal infection to determine whether preexposure, eliciting the lymphocyte-dependent response, was species specific. Results. E coli preexposure alone caused no Th1 or Th2 shift; increased the proliferative responses of T cells; and, in combination with IL-12 therapy, caused markedly decreased IL-2 and IL-4 responses and an increased IFN-γ response. IL-12 therapy did not change the response to intra-abdominal infection despite its ability to cause marked Th1 polarization. IFN-γ-deficient mice responded to E coli preexposure no differently than did wild-type mice. Transfer of lymphocytes preexposed to Pseudomonas aeruginosa, Klebsiella pneumoniae, and hemolytic E coli but not other types of nosocomial pathogens caused the development of more abscesses just as transfer of E coli preexposed lymphocytes had. Conclusions. 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 Enterobacteriaceae alters responses to intra-abdominal infection.
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U2 - 10.1016/S0039-6060(98)70149-7
DO - 10.1016/S0039-6060(98)70149-7
M3 - Article
C2 - 9706167
AN - SCOPUS:0031858244
SN - 0039-6060
VL - 124
SP - 418
EP - 428
JO - Surgery
JF - Surgery
IS - 2
ER -