Association of CD4+ T cell-dependent keratitis with genetic susceptibility to Pseudomonas aeruginosa ocular infection.
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.
Kwon
B
B
Department of Anatomy/Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Hazlett
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LD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004198:Disease Susceptibility; D007113:Immunity, Innate; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000276:immunology; D007634:Keratitis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011552:Pseudomonas Infections / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D013194:Staining and Labeling; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
D000911:Antibodies, Monoclonal; D001613:beta 2-Microglobulin; D007371:Interferon-gamma