Host priming, not target antigen type, decides rejection rate in mice primed with MHC II 'knockout' cultured keratinocytes

J. P. Hunt, C. T. Hunter, M. Brownstein, C. S. Hultman, S. DeSerres, L. Bracey, Jeffrey A Frelinger, A. A. Meyer

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)32-36
Number of pages5
JournalJournal of Surgical Research
Volume76
Issue number1
DOIs
StatePublished - Apr 1998
Externally publishedYes

Fingerprint

Major Histocompatibility Complex
Keratinocytes
Allografts
Antigens
Tail
Transplants
Graft Survival
Autografts
Graft Rejection
Burns
Inbred CBA Mouse
Alopecia
Heterografts
Color
Skin
Wounds and Injuries

Keywords

  • Burns
  • Cultured keratinocytes
  • Major histocompatibility complex II knockout mice
  • Second set rejection
  • Skin graft

ASJC Scopus subject areas

  • Surgery

Cite this

Hunt, J. P., Hunter, C. T., Brownstein, M., Hultman, C. S., DeSerres, S., Bracey, L., ... Meyer, A. A. (1998). Host priming, not target antigen type, decides rejection rate in mice primed with MHC II 'knockout' cultured keratinocytes. Journal of Surgical Research, 76(1), 32-36. https://doi.org/10.1006/jsre.1998.5278

Host priming, not target antigen type, decides rejection rate in mice primed with MHC II 'knockout' cultured keratinocytes. / Hunt, J. P.; Hunter, C. T.; Brownstein, M.; Hultman, C. S.; DeSerres, S.; Bracey, L.; Frelinger, Jeffrey A; Meyer, A. A.

In: Journal of Surgical Research, Vol. 76, No. 1, 04.1998, p. 32-36.

Research output: Contribution to journalArticle

Hunt, J. P. ; Hunter, C. T. ; Brownstein, M. ; Hultman, C. S. ; DeSerres, S. ; Bracey, L. ; Frelinger, Jeffrey A ; Meyer, A. A. / Host priming, not target antigen type, decides rejection rate in mice primed with MHC II 'knockout' cultured keratinocytes. In: Journal of Surgical Research. 1998 ; Vol. 76, No. 1. pp. 32-36.
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abstract = "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.",
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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, Jeffrey A

AU - Meyer, A. A.

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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.

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KW - Major histocompatibility complex II knockout mice

KW - Second set rejection

KW - Skin graft

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