Cellular and Humoral Effector Mechanisms of Acute Cardiac Allograft Rejection in a Rat Model

Morton, A. Lawrie (1992) Cellular and Humoral Effector Mechanisms of Acute Cardiac Allograft Rejection in a Rat Model. MD thesis, University of Glasgow.

Abstract

This thesis examines the role played by CD4+ and CD8+ T cells in the rejection of a class I disparate cardiac allograft in a rat model (R8---RT1u). The effector mechanisms involved in the rejection process are studied, and particular emphasis given to the possibility of specific alloantibody acting as an effector of acute allograft rejection. Following the establishment of the rejection times of a class I disparate, heterotopic, intra-abdominal, cardiac allograft in unmodified animals, manipulation of T cell subsets in the recipient animals was achieved in vivo by the administration of mouse anti-rat monoclonal antibodies specific for either the CD4 or the CD8 molecule. Depletion of CDS8+ T cells had no effect on graft survival whereas CD4+ T cell depletion resulted in prolonged allograft survival. In addition, the acceptance of the class I disparate graft following anti-CD4 monoclonal antibody treatment was associated with the abrogation of the specific alloantibody response against the donor tissue seen in unmodified rejection and in the anti-CD8 treated group. Anti-class I alloantibody was shown to specifically lyse in vitro cultures of donor cardiac endothelial cells and passive transfer of immune serum in vivo results in the restoration of acute rejection in an animal depleted of CD4+ T cells. This calls into question the accepted belief that the CD8+ T cell is of crucial importance in the acute rejection of a class I disparate allograft, by its role as a cytotoxic T cell. The CDS8+ T cell is not required for the rejection of such a graft in this model. On the contrary, the CD4+ T cell was found to be essential to the rejection process and the findings of the alloantibody experiments suggest that the CD4+ T cell is mediating acute rejection by providing T cell help for the production of specific, cytotoxic alloantibody. The significant finding of the rejection of a class I disparate allograft in the absence of CD8+ T cells provides further support for the indirect pathway of allorecognition.

• Item Type: Thesis (MD)
• Qualification Level: Doctoral
• Additional Information: Adviser: Andrew J Bradley
• Keywords: Medicine, Immunology
• Date of Award: 1992
• Depositing User: Enlighten Team
• Unique ID: glathesis:1992-74542
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 27 Sep 2019 17:51
• Last Modified: 27 Sep 2019 17:51
• URI: https://theses.gla.ac.uk/id/eprint/74542