Document Detail

The cellular basis of cardiac allograft rejection: VIII. Mechanisms underlying delayed allograft rejection in PVG C6-deficient rats.
MedLine Citation:
PMID:  9603160     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The delayed allograft rejection in C6-deficient PVG C6- rats compared with normal PVG rats has been attributed to the lack of alloantibody activation of the membrane attack complex of complement. As T cells alone have been shown to effect graft rejection, we examined T-cell responses in PVG C6- rats. METHODS: The cellular infiltrate and its mRNA for cytokines and effector molecules in DA heart allografts to PVG and PVG C6- rats was compared by immunoperoxidase staining and semiquantitative reverse transcriptase polymerase chain reaction. The ability of pure populations of T cells or alloantibody to mediate DA heart graft rejection in irradiated (750 rads) PVG and PVG C6- rats was also compared. RESULTS: The median rejection time of DA heart allografts was 8 days in PVG rats and 17.5 days in PVG C6-. PVG C6- rats sensitized to DA by two skin grafts rejected DA heart grafts in 5-6 days. CD3+, CD4+, CD8+, interleukin-2 receptor-positive T cell, macrophage, and natural killer cell infiltration, as well as class II major histocompatibility complex and intercellular adhesion molecule-1 up-regulation, in grafts was similar in naive PVG and PVG C6- rats. mRNA for T helper 1 cytokine interleukin-2, interferon-gamma, tumor necrosis factor-beta, macrophage molecules tumor necrosis factor-alpha, and inducible nitric oxide synthase, as well as cytotoxic T-cell effector molecules perforin and granzyme A and B, were found to be the same in the grafts from both naive PVG and naive PVG C6- rats. Thus, there appeared to be no difference in the T-cell effector response between the PVG and PVG C6- groups. There were higher alloantibody titers in PVG C6- rats than in PVG hosts. Irradiation ablated rejection and alloantibody responses and reconstitution with naive T cells alone restored rejection in both PVG and PVG C6- rats. Irradiated rats given serum from PVG rats that had rejected DA grafts did not effect rejection of DA grafts even if given naive T cells. Sensitized T cells restored second set. CONCLUSIONS: PVG C6- rats have normal T-cell responses and can mediate allograft rejection in the absence of alloantibody. The failure of PVG C6- to reject allografts rapidly may be a result of the poor clearance of alloantisera leading to enhancement of graft survival rather than a critical role for complement and membrane attack complex in acute rejection.
S Merten; J C Chen; H Ha; K Plain; R A Boyd; M J Penny; P Leenaerts; B M Hall
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplantation     Volume:  65     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  1998 May 
Date Detail:
Created Date:  1998-06-19     Completed Date:  1998-06-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1152-8     Citation Subset:  IM    
Department of Medicine, University of New South Wales, Liverpool Hospital, Australia.
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MeSH Terms
Complement C6 / deficiency
Cytokines / genetics
Graft Rejection / pathology*
Graft Survival / immunology
Heart Transplantation*
Isoantibodies / immunology
RNA, Messenger / metabolism
Rats, Inbred Strains
Rats, Mutant Strains / blood
Reference Values
T-Lymphocytes / physiology
Time Factors
Transplantation, Homologous
Whole-Body Irradiation
Reg. No./Substance:
0/Complement C6; 0/Cytokines; 0/Isoantibodies; 0/RNA, Messenger
Comment In:
Transplantation. 1999 Jun 15;67(11):1498-9   [PMID:  10385097 ]

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