MECHANISMS OF T CELL MIGRATION TO VASCULARIZED ORGAN TRANSPLANTS

Walch, Jeffrey (2014) MECHANISMS OF T CELL MIGRATION TO VASCULARIZED ORGAN TRANSPLANTS. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

A critical event in the rejection of transplanted organs is the migration of effector or memory T cells to the graft. The prevailing view is that the key steps involved in this process, integrin-mediated firm adhesion followed by transendothelial migration, are dependent on the activation of Gαi-coupled chemokine receptors on T cells. In contrast to this view, we demonstrate in vivo that cognate antigen is necessary for the firm adhesion and transendothelial migration of CD8+ effector T cells specific to graft antigens and that both steps occur independent of Gαi signaling. Presentation of cognate antigen by either graft endothelial cells or bone marrow derived antigen presenting cells that extend into the capillary lumen was sufficient for T cell migration. The adhesion and transmigration of antigen non-specific (bystander) effector T cells, on the other hand, remained dependent on Gαi but required the presence of antigen-specific effector T cells. These findings underscore the primary role of cognate antigen presented by either endothelial or bone marrow derived antigen-presenting cells in the migration of T cells across endothelial barriers and have important implications for the prevention and treatment of graft rejection.

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Details

Item Type:	University of Pittsburgh ETD
Status:	Unpublished
Creators/Authors:	Creators Email Pitt Username ORCID Walch, Jeffrey walch.jeff@gmail.com
ETD Committee:	Title Member Email Address Pitt Username ORCID Thesis Advisor Lakkis, Fadi lakkisf@upmc.edu FGL1 Committee Member Chalasani, Geetha gec12@pitt.edu GEC12 Committee Member Kalinski, Pawel pak5@pitt.edu PAK5 Committee Member Kane, Lawrence lkane@pitt.edu LKANE Committee Member Lagasse, Eric lagasse@pitt.edu LAGASSE
Date:	1 April 2014
Date Type:	Publication
Defense Date:	14 March 2103
Approval Date:	1 April 2013
Submission Date:	29 March 2013
Access Restriction:	5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages:	86
Institution:	University of Pittsburgh
Schools and Programs:	School of Medicine > Immunology
Degree:	PhD - Doctor of Philosophy
Thesis Type:	Doctoral Dissertation
Refereed:	Yes
Uncontrolled Keywords:	The focus of this work is to understand how our immune cells are able to migrate into a transplanted organ before hurting that tissue.
Date Deposited:	01 Apr 2013 13:46
Last Modified:	01 Apr 2018 05:15
URI:	http://d-scholarship.pitt.edu/id/eprint/17989

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