TY - JOUR
T1 - Host priming, not target antigen type, decides rejection rate in mice primed with MHC II 'knockout' cultured keratinocytes
AU - Hunt, J. P.
AU - Hunter, C. T.
AU - Brownstein, M.
AU - Hultman, C. S.
AU - DeSerres, S.
AU - Bracey, L.
AU - Frelinger, J.
AU - Meyer, A. A.
PY - 1998/4
Y1 - 1998/4
N2 - 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.
AB - 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.
KW - Burns
KW - Cultured keratinocytes
KW - Major histocompatibility complex II knockout mice
KW - Second set rejection
KW - Skin graft
UR - http://www.scopus.com/inward/record.url?scp=0031928148&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031928148&partnerID=8YFLogxK
U2 - 10.1006/jsre.1998.5278
DO - 10.1006/jsre.1998.5278
M3 - Article
C2 - 9695735
AN - SCOPUS:0031928148
SN - 0022-4804
VL - 76
SP - 32
EP - 36
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 1
ER -