Antibody-mediated chronic rejection in CD52 transgenic mice after T cell depletion with alemtuzumab Öffentlichkeit
Kim, Dong Won (2012)
Published
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
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