USE OF INTEGRIN BLOCKADE TO INHIBIT CD8+ MEMORY T CELLS IN SOLID ORGAN TRANSPLANTATION Public

Abstract

ABSTRACT


USE OF INTEGRIN BLOCKADE TO INHIBIT CD8+ T CELLS IN SOLID
ORGAN TRANSPLANTATION

By: Divya Haridas


Although calcineurin-based inhibitors have come a long way in inhibiting organ
rejection, the associated toxicities have led to the continued quest for better
immunosuppressants. Two potential candidates are belatacept and efalizumab. Belatacept
is a costimulation blocker that has been shown to have higher acute rejection rates in
kidney transplant patients compared to traditional calcineurin inhibitors. Here we
hypothesize and show that belatacept had no effect on the cytokine production of
memory CD8+ T cells. Efalizumab binds the integrin LFA-1 and blocks the LFA-1-
ICAM-1 interaction crucial for T cell activation and trafficking. We show here that
efalizumab was effective in inhibiting alloreactive memory CD8 T cell responses. We
also found that graft-elicited CD8+ T cells were inhibited by anti-LFA-1 but not
pathogen-elicited T cells. Thus, the susceptibility of T cells to different
immunosuppressants is different based on their priming conditions and this warrants
further investigation.

Table of Contents

Introduction 1

Types of Graft Rejection 1

History of Immunosuppression 2

Important Immunosuppressive Drugs And Their Side Effects 2

Development and Efficacy of Belatacept 3

Methods 6

Results 7

Discussion 10

Figures 12

References 21

About this Master's Thesis

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Degree	MS
Submission	Master's Thesis
Language	English
Research Field	Biology, General
Mot-clé	Transplantation Integrin blockade Anti-LFA-1 Memory CD8+
Committee Chair / Thesis Advisor	Ford, Mandy L, Emory University
Committee Members	Iwakoshi, Neal N., Emory University Steinhauer, David, Emory University Mittler, Robert S, Emory University

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