Bacterially preexposed T cells impair bacterial elimination by non-Th1/Th2 cell mechanisms in a model of intra-abdominal infection.
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.
Gleason
T G
TG
Surgical Infectious Disease Laboratory, University of Virginia, Charlottesville 22908, USA.
Sawyer
R G
RG
Pruett
T L
TL
D018784:Abdominal Abscess / Q000276:immunology* / Q000382:microbiology; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D000946:Antigens, Fungal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000382:microbiology*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000382:microbiology; D002177:Candidiasis / Q000188:drug therapy / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000276:immunology*; D005434:Flow Cytometry; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000276:immunology; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000942:Antigens, Bacterial; D000946:Antigens, Fungal; D018664:Interleukin-12; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens