Bacterially preexposed T cells impair bacterial elimination by non-Th1/Th2 cell mechanisms in a model of intra-abdominal infection.

Abstract

BACKGROUND:

Escherichia coli preexposure in mice results in impaired elimination of subsequent intra-abdominal infections by a CD+4 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-gamma (INF-gamma)-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-gamma response. IL-12 therapy did not change the response to intra-abdominal infection despite its ability to cause marked Th1 polarization. IFN-gamma-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.

• Authors: T G Gleason, R G Sawyer, T L Pruett
• Journal: Surgery (Surgery) Vol. 124 Issue 2 Pg. 418-28 (Aug 1998) ISSN: 0039-6060 [Print] United States
• PMID: 9706167 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Bacterial
• Antigens, Fungal
• Interleukin-12
• Interferon-gamma
• Leukocyte Common Antigens

Topics

• Abdominal Abscess (immunology, microbiology)
• Animals
• Antigens, Bacterial (immunology)
• Antigens, Fungal (immunology)
• CD4-Positive T-Lymphocytes (chemistry, immunology, microbiology)
• CD8-Positive T-Lymphocytes (chemistry, immunology, microbiology)
• Candidiasis (drug therapy, immunology)
• Escherichia coli (immunology)
• Escherichia coli Infections (drug therapy, immunology)
• Flow Cytometry
• Immunophenotyping
• Interferon-gamma (pharmacology)
• Interleukin-12 (pharmacology)
• Leukocyte Common Antigens (analysis)
• Mice
• Mice, Inbred BALB C
• Pseudomonas Infections (drug therapy, immunology)
• Species Specificity
• Spleen (cytology, immunology)