BURN INJURY IMPAIRS 2ND-SET REJECTION AND CTL REACTIVITY IN MICE PRIMED BY CULTURED KERATINOCYTE ALLOGRAFTS

Cultured keratinocyte (CK) allografts have limited antigenicity and ha ve been used as a skin replacement in patients with massive thermal in jury, Recent data indicate that CK grafts are more immunogenic than pr eviously believed and could compromise wound healing in the immunocomp etent host. The purpose of this study was to determine if the immunosu ppression of burn injury might affect the alloantigen response and min imize sensitization to CK allografts. CBA mice received a 0%, 20%, or 40% burn that was partially excised three days later and grafted with a full-thickness (FT) skin allograft, CK allograft, or CK autograft. T wo weeks postburn, mice received FT tail skin allografts, which were o bserved for rejection. We observed that FT and CK allografts primed th e unburned host with equal efficacy. However, burn injury selectively minimized priming by CK allografts, resulting in delayed rejection of second-set allografts. With evidence that burn injury inhibits host se nsitization to CK allografts, we then examined the effect of burn size on CTL alloreactivity. Additional CBA mice underwent burn injury, exc ision, and grafting as described above. Host splenocytes were harveste d two weeks later and tested on radiolabeled targets for allospecific cytotoxicity. CTLs from unburned mice primed with FT allografts demons trated the greatest CTL lysis, followed next by CTLs from unburned mic e covered with CK allografts. Burn injury inhibited CTL activity as a function of wound size. Activity of CTLs from burned mice primed with CK allografts improved after in vitro allostimulation but remained bel ow that of CTLs from unburned, unprimed mice. We conclude that burn in jury selectively inhibits the allospecific response to CK allografts. The decreased immunogenicity of CK allografts, when used for burn woun d coverage, may improve the long-term survival of allogeneic keratinoc ytes, enhancing their potential as a biologic skin replacement.