Association of CD4+ T cell-dependent keratitis with genetic susceptibility to Pseudomonas aeruginosa ocular infection

J Immunol. 1997 Dec 15;159(12):6283-90.

Abstract

The role of T lymphocytes in susceptibility to Pseudomonas aeruginosa corneal infection was studied in inbred C57Bl/6 (B6) beta2-microglobulin+/+ (beta2m+/+) and beta2m-/- knockout (KO) mice on a B6 genetic background. The corneas of both B6 and KO mice perforated by 7 days postinfection (p.i.). Histopathology revealed a similar inflammatory response characterized by an infiltration of polymorphonuclear neutrophilic leukocytes by 24 h p.i. in both groups of mice. CD4+ and CD8+ (latter absent in KO) T cells were present in cornea by 3 days p.i., and by 5 days, IL-2R-positive cells were positively immunostained. Corneas of B6 beta2m+/+ mice depleted of CD4+ T cells and infected with P. aeruginosa did not perforate at 7 days p.i. vs mice depleted of CD8+ T cells or treated with an irrelevant mAb. Neutralization of IFN-gamma before infecting B6 mice prevented corneal perforation and was associated with a lower delayed-type hypersensitivity than in B6 mice similarly treated with an irrelevant mAb. These data provide evidence that a CD4+ T cell (Th1)-dominated response following P. aeruginosa corneal infection is associated with genetic susceptibility and corneal perforation in inbred B6 mice.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • CD4-Positive T-Lymphocytes / immunology*
  • Disease Susceptibility
  • Immunity, Innate
  • Immunohistochemistry
  • Injections, Intraperitoneal
  • Interferon-gamma / immunology
  • Keratitis / genetics*
  • Keratitis / immunology*
  • Keratitis / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pseudomonas Infections / genetics*
  • Pseudomonas Infections / immunology*
  • Pseudomonas Infections / pathology
  • Staining and Labeling
  • beta 2-Microglobulin / deficiency
  • beta 2-Microglobulin / genetics

Substances

  • Antibodies, Monoclonal
  • beta 2-Microglobulin
  • Interferon-gamma