Host priming, not target antigen type, decides rejection rate in mice primed with MHC II "knockout" cultured keratinocytes.
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 tail-graft 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.
Department of Surgery and Immunology, University of North Carolina at Chapel Hill, USA.
J P
JP
Hunt
C T
CT
Hunter
M
M
Brownstein
C S
CS
Hultman
S
S
deSerres
L
L
Bracey
J
J
Frelinger
A A
AA
Meyer
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002056:Burns / Q000276:immunology / Q000628:therapy; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D015603:Keratinocytes / Q000737:chemistry* / Q000276:immunology / Q000637:transplantation*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D016296:Mutagenesis / Q000502:physiology; D016038:Skin Transplantation / Q000276:immunology / Q000379:methods*; D013623:Tail
D000949:Histocompatibility Antigens Class II