title: The 1995 Moyer Award. The effect of burn injury on allograft rejection, alloantigen processing, and cytotoxic T-lymphocyte sensitization.
abstract: Burn injury impairs cellular immunity, increases the risk of viral infection, and delays allograft rejection, but little is known about its effect on antigen processing and cytotoxic T-lymphocyte (CTL) function. This study examined the effect of burn injury on alloantigen sensitization with an in vivo model of second-set rejection and in vitro assays of CTL alloreactivity. Anesthetized CBA mice (n = 95) received a 0%, 20%, or 40% full-thickness contact burn that was partially excised 3 days later and covered with autograft or C57BL/6 allograft. Two weeks after the burn was inflicted, mice were challenged with second-set tail allografts, which were observed for rejection. Median graft survival times were compared by Wilcoxon rank and chi-squared analysis. Additional CBA mice (n = 24) underwent similar burn injury, excision, and grafting. Splenocytes were harvested 2 weeks later and were used as CTL effectors against radiolabeled targets. Dilution curves of target lysis were compared by analysis of variance. Forty percent burn injury prolonged unprimed allograft survival from 13 to 15 days (p < 0.01) but had a greater effect on primed allograft survival, which increased from 9 to 12.5 days (p < 0.01). Furthermore, a 40% burn eliminated the influence of priming, resulting in second-set graft survival similar to that of mice in an unburned, unprimed control group (12.5 vs. 13 days, NS). Whereas 20% burn injury did not inhibit CTL priming, a 40% burn profoundly impaired CTL function (p < 0.001), which recovered only after 6 days of in vitro allostimulation. Burn injury inhibits both alloantigen priming and the immunologic memory of CTLs as a function of burn size. This impairment in alloantigen processing helps to explain defects in cellular immunity and suggests a mechanism for prolonged allograft survival and decreased viral resistance after burn injury occurs.
authors.affiliation: Department of Surgery, University of North Carolina, Chapel Hill 27599-7210, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Hultman
authors.forename: B A
authors.initials: BA
authors.lastname: Cairns
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.forename: S
authors.initials: S
authors.lastname: deSerres
authors.forename: J A
authors.initials: JA
authors.lastname: Frelinger
authors.forename: A A
authors.initials: AA
authors.lastname: Meyer
mesh_terms: D000818:Animals; D001363:Awards and Prizes; D002056:Burns / Q000276:immunology* / Q000628:therapy; D016009:Chi-Square Distribution; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival / Q000276:immunology; D006649:Histocompatibility Antigens / Q000276:immunology; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016378:Tissue Transplantation / Q000473:pathology / Q000502:physiology; D014181:Transplantation Immunology / Q000276:immunology*
chemical_list: D006649:Histocompatibility Antigens; D007519:Isoantigens