Immunogenicity of cultured keratinocyte allografts deficient in major histocompatibility complex antigens

C. Scott Hultman, John P. Hunt, Hiromasa Yamamoto, Athina Giannopoulos, Suzan DeSerres, Jeffrey A. Frelinger, Anthony A. Meyer

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: Full-thickness (FT) and cultured keratinocyte (CK) allografts have been used as temporary skin replacements in patients with massive burns, but these grafts are ultimately rejected after restoration of host immunocompetence. Genetic engineering has permitted the creation of knockout (KO) mice deficient in class I or class II major histocompatibility antigens. This study examines the immunogenicity of such grafts to determine if these genetically modified keratinocytes could be used for permanent wound coverage. Methods: Host sensitization to alloantigen was assessed by second- set rejection. CBA mice (n = 111) were primed with flank grafts consisting of FT and CK allografts from normal C57BL/6 donors, FT and CK class I KO allografts, FT and CK class II KO allografts, and CK autografts. Three weeks later, hosts were challenged with normal tail allografts and observed for second-set rejection. Median graft survival was analyzed by X2 and Wilcoxon rank tests. In the second experiment, cytotoxic T lymphocytes (CTLs) were harvested from CBA mice (n = 28) 3 weeks after flank grafting. CTL effectors were tested on radiolabeled targets at various ratios in a 51Cr release assay. Dilution curves of CTL activity were compared by analysis of variance. Results: Hosts primed with CK or FT allografts demonstrated accelerated rejection of second-set tail grafts compared with hosts covered with CBA autografts. CK knockout grafts were less immunogenic than FT knockout skin; class II KO allografts were considerably less immunogenic than class I KO allografts. CTL activity against the knockout CK allografts was negligible compared with that of hosts primed with normal allografts or FT knockout allografts. Conclusion: Although full-thickness knockout skin retains substantial immunogenicity, cultured keratinocytes deficient in class II antigens fail to prime for accelerated second-set rejection and do not elicit a CTL response in the graft recipient. This lack of immunogenicity may permit the indefinite survival of allogeneic knockout keratinocytes in patients requiring massive wound excision and coverage.

Original languageEnglish (US)
Pages (from-to)25-34
Number of pages10
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume45
Issue number1
DOIs
StatePublished - Jul 1998
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

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