Antibody-mediated chronic rejection in CD52 transgenic mice after T cell depletion with alemtuzumab Pubblico

Abstract

Alemtuzumab, with its ability to provide profound T-cell depletion without major side effects,
looks promising as it can potentially reduce the amount of calcineurin inhibitors used in
transplant patients. Unfortunately, the lack of understanding about the mechanisms of
alloreactive T-cell repopulation and antibody-mediated rejection remains an unsolved issue in
the clinical care of patients after alemtuzumab treatment. In this study, using human CD52
transgenic mice treated with alemtuzumab, we performed detailed examinations of graft survival,
level of serum alloantibody, and the effects of lymphocyte depletion on the development of
antibody-mediated chronic rejection. Fully MHC-class mismatched donor cardiac allografts were
transplanted into alemtuzumab-treated CD52Tg mice and showed no acute rejection for 200 days
after transplantation while untreated recipients acutely rejected their grafts within 10 days after
transplantation. However, approximately half of long-term alemtuzumab-treated mice showed
increased degrees of vasculopathy and C3d deposition at day 100 post-transplant. The
histological development of chronic rejection correlated with donor-specific alloantibody
production and C3d deposition in the graft. Furthermore, alloreactive B cells were shown to
increase in accordance with Donor Specific Antibody detection (DSA). The potential
significance of this work is not only to elucidate the mechanisms that govern a humoral
component of the immune response but also to create a discriminating model in which in vivo
data of antibody-mediated chronic rejection can be studied.

Table of Contents

Table of Contents

Section







Page number
I.
Introduction





1 - 7
II.
Methods






8 - 11
III.
Results






12 - 25
IV.
Discussion






26 - 31
V.
Future applications of current results


32 - 33
VI.
Acknowledgements




33
VII.
References






34 - 38

About this Honors Thesis

Rights statement

• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Emory College
Department	Biology
Degree	BS
Submission	Honors Thesis
Language	English
Research Field	Biology, General
Parola chiave	Transplant Immunology
Committee Chair / Thesis Advisor	Knechtle, Stuart J, Emory University
Committee Members	Campbell, Kathleen, Emory University Morkin, Tracy, Emory University Starnes, Amanda, Emory University

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