An MHC class II disparity raises the threshold for tolerance induction in pulmonary allografts in miniature swine.

An MHC class II disparity raises the threshold for tolerance induction in pulmonary allografts in miniature swine. Research Abstract Details 

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An MHC class II disparity raises the threshold for tolerance induction in pulmonary allografts in miniature swine. Abstract Text:

T Shoji,H Sahara,A Muniappan,D A Guenther,S L Houser,A C Pujara,M A Bravard,J C Wain,D H Sachs,J C Madsen,J S Allan,

OBJECTIVES: The mechanisms and treatment of chronic rejection in pulmonary allotransplantation remain elusive. We have induced robust tolerance to class I-disparate lung allografts in miniature swine using an intensive 12-day course of tacrolimus. Here, we tested whether a tolerant state can be induced in swine receiving fully mismatched lung allografts. METHODS: Orthotopic left lung allografts were performed using MHC class I-disparate (group 1: n = 3) or fully disparate (group 2: n = 6) donors. The recipients received a 12-day postoperative course of tacrolimus (continuous intravenous infusion; target level = 35-50 ng/mL) as their only immunosuppression. RESULTS: All swine in group 1 maintained their grafts long term without developing any lesions of chronic rejection (>497, >432, >451 days). These recipients exhibited donor-specific hyporesponsiveness in cell-mediated lymphocytotoxity (CML) and mixed lymphocyte reaction (MLR) assays. In group 2, five of the six recipients maintained their grafts long term (sacrificed on postoperative days 515, 389, 429, 481, and 438 with viable grafts). Isolated lesions of obliterative bronchiolitis were occasionally seen on biopsy, and donor-specific hyporesponsiveness on assays was consistently observed. The remaining recipient rejected its graft on day 103 with histologic findings of obliterative bronchiolitis. CONCLUSIONS: We report long-term graft acceptance without chronic immunosuppression in five of six recipients across a full MHC disparity, albeit with some evidence of obliterative bronchiolitis. These data suggest that the class II disparity inherent in a fully mismatched transplant increases the requirement for tolerance induction.

An MHC class II disparity raises the threshold for tolerance induction in pulmonary allografts in miniature swine. Publishing Authors By Initials

T Shoji,H Sahara,A Muniappan,DA Guenther,SL Houser,AC Pujara,MA Bravard,JC Wain,DH Sachs,JC Madsen,JS Allan,

For similar surgical procedures, operative: transplantation: transplantation, homologous research abstracts see: surgical procedures, operative: transplantation: transplantation, homologous research

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An MHC class II disparity raises the threshold for tolerance induction in pulmonary allografts in miniature swine. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Transplantation proceedings

VOLUME: 38

Page Numbers: 3268-70

Journal Abbreviation: Transplant. Proc.

ISSN: 0041-1345

DAY: 3

MONTH: Dec

YEAR: 2006

An MHC class II disparity raises the threshold for tolerance induction in pulmonary allografts in miniature swine. Information

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LANGUAGE: eng

NlmUniqueID: 243532

An MHC class II disparity raises the threshold for tolerance induction in pulmonary allografts in miniature swine. Keywords Mesh Terms:

KEYWORDS: Transplantation, Homologous

MESH TERMS: immunology

Chemical & Substance for Abstract: An MHC class II disparity raises the threshold for tolerance induction in pulmonary allografts in miniature swine. Information

Substance Name: Histocompatibility Antigens Class II

Registry Number: 0

Grant and Affiliation Information for An MHC class II disparity raises the threshold for tolerance induction in pulmonary allografts in miniature swine.

AFFILIATION: Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: R01 HL067110-04

ACRONYM: HL

MEDLINETA: Transplant Proc

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