Host Priming, Not Target Antigen Type, Decides Rejection Rate in Mice Primed with MHC II “Knockout” Cultured Keratinocytes

• Published in: The Journal of surgical research 1998-04, Vol.76 (1), p.32-36
• Main Authors: Hunt, J.P., Hunter, C.T., Brownstein, M., Hultman, C.S., deSerres, S., Bracey, L., Frelinger, J., Meyer, A.A.
• Format: Article
• Language: English
• Subjects: Animals; Antigen Presentation - immunology; Biological and medical sciences; burns; Burns - immunology; Burns - therapy; Cells, Cultured; cultured keratinocytes; Female; Gene Expression - physiology; Graft Rejection - immunology; Graft Survival - immunology; Histocompatibility Antigens Class II - genetics; Keratinocytes - chemistry; Keratinocytes - immunology; Keratinocytes - transplantation; major histocompatibility complex II knockout mice; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Mutagenesis - physiology; second set rejection; skin graft; Skin plastic surgery; Skin Transplantation - immunology; Skin Transplantation - methods; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tail
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1998.5278

Background.Lack of skin for autograft continues to be problematic in patients with large burns. Allograft and xenograft have been used, but are prone to rapid rejection. Use of cultured keratinocytes (CK) and major histocompatibility complex (MHC) II “knockout” grafts leads to prolonged graft survival compared to allograft. Whether this prolongation is secondary to decreased priming efficacy or target recognition is unknown. Whether a combination of these techniques would generate a less immunogenic allograft remains to be determined. Methods.CBA mice (n= 100) were flank-grafted with full thickness C57BL/6 (B6 FT), B6 cultured keratinocytes (B6 CK), B6 major histocompatibility complex II “knockout” full thickness (KO II FT), B6 major histocompatibility complex II “knockout” cultured keratinocytes (KO II CK), or a full thickness autograft (Auto). Three weeks after priming flank grafting, B6, MHC I (KO I), and KO II full thickness tail grafts were placed on each mouse. Tail graft rejection was assessed daily by an observer blinded to flank and tailgraft type. A 4-point grading system for graft color, hair loss, and texture was used. Results.Animals primed with KO II CK flank grafts had increased survival of tail grafts over B6 FT flank grafted controls (12.3 ± 1.05 vs 10.1 ± 1.00,P< 0.05). Within flank graft groups, however, B6, KO I, and KO II tail graft survival was similar. Conclusions.KO II CK allografts decrease host priming compared to normal B6 FT allograft. MHC deletion (KO I or KO II) does not protect a target graft from rejection in a primed host. CK and KO techniques may offer a less immunogenic allograft and a readily available source of wound coverage in patients with extensive burns.