Anti-CD2 Mediated Prolongation of Allograft Survival

Stell, David Andrew (2001) Anti-CD2 Mediated Prolongation of Allograft Survival. PhD thesis, University of Glasgow.

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The CD2 molecule is a cell surface glycoprotein expressed on rat T cells which has numerous functions including the provision of a TCR-independent pathway of T cell activation, costimulation in T cell activation via the TCR, intercellular adhesion and the transmission of negative signals. Murine studies have shown that targeting the CD2 molecule with mAh has potent immunological effects including the prolongation of allograft survival. In this project I have assessed the effects of the mouse anti-rat CD2 mAh OX34 and OX55 in transplant models. OX34 proved to be more effective than OX55 in the low responder Lewis to DA strain combination, and this prolonged graft survival was associated with greater depletion of CD4 T cells by OX34. Analysis of the time course and distribution of depletion in different lymphocyte compartments suggested that host factors are also involved in OX34-mediated depletion. Despite the potent effects of OX34 in transplant models it has little effect on in vitro allogeneic models compared to those of anti-CD4 mAb. In particular OX34 does not affect proliferation and release of Th1 cytokines in the MLR and does not prevent anti-TCR-mediated T cell activation. The principal effect of OX34 appears therefore to be depletion of T cells, an effect which is not reproduced in in vitro systems. OX34 mAb was also found to have a synergistic action with both the anti-CD4 mAb 0X38 and CTLA4lg. Both of these combinations were able to induce permanent allograft survival in the high responder DA to Lewis combination. Graft survival in these models is associated with abrogation of the anti- globlin response combined with profound and prolonged T cell depletion. Evidence is presented therefore that, in contrast to murine studies, the principle effect of anti- CD2 mAb in rat transplant models is immunosuppression by T cell depletion mediated by the delivery of negative signals.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: Eleanor Bolton
Keywords: Medicine, Surgery, Immunology
Date of Award: 2001
Depositing User: Enlighten Team
Unique ID: glathesis:2001-76143
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 16:35
Last Modified: 19 Nov 2019 16:35

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