Donor T-cell alloreactivity against host thymic epithelium limits T-cell development after bone marrow transplantation.

Abstract:

:Acute graft-versus-host disease (aGVHD) impairs thymus-dependent T-cell regeneration in recipients of allogeneic bone marrow transplants through yet to be defined mechanisms. Here, we demonstrate in mice that MHC-mismatched donor T cells home into the thymus of unconditioned recipients. There, activated donor T cells secrete IFN-gamma, which in turn stimulates the programmed cell death of thymic epithelial cells (TECs). Because TECs themselves are competent and sufficient to prime naive allospecific T cells and to elicit their effector function, the elimination of host-type professional antigen-presenting cells (APCs) does not prevent donor T-cell activation and TEC apoptosis, thus precluding normal thymopoiesis in transplant recipients. Hence, strategies that protect TECs may be necessary to improve immune reconstitution following allogeneic bone marrow transplantation.

journal_name

Blood

journal_title

Blood

authors

Hauri-Hohl MM,Keller MP,Gill J,Hafen K,Pachlatko E,Boulay T,Peter A,Holländer GA,Krenger W

doi

10.1182/blood-2006-07-034157

subject

Has Abstract

pub_date

2007-05-01 00:00:00

pages

4080-8

issue

9

eissn

0006-4971

issn

1528-0020

pii

blood-2006-07-034157

journal_volume

109

pub_type

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