help button home button Am J Pathol ASIP 2008 Summer Academy, Molecular Methcanisms of Human Disease: Injury, Inflammation, and Tissue Repair
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Order Full text via Infotrieve
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Surh, C. D.
Right arrow Articles by Sprent, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Surh, C. D.
Right arrow Articles by Sprent, J.

American Journal of Pathology, Vol 151, 591-599, Copyright © 1997 by American Society for Investigative Pathology

REGULAR ARTICLES

Rat stem cells developing in irradiated SCID mice fail to become tolerized and cause lethal graft-versus-host disease

CD Surh, H Kosaka and J Sprent
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.

Graft-versus-host disease (GVHD) is prominent in irradiated hosts given whole allogeneic bone marrow cells but is generally undetectable when T- depleted stem cells are transferred; under these conditions, the mature T cells arising from the donor stem cells become tolerant to host antigens and fall to cause GVHD. We show here that a radically different situation can occur when hosts are reconstituted with xenogeneic stem cells. When lightly irradiated, adult C.B-17 SCID mice injected with Lewis rat fetal liver (FL) cells show near-total repopulation with rat-derived lymphohemopoietic cells, including T and B cells. However, in marked contrast to chimeras prepared with allogeneic mouse FL cells, rat FL-->SCID chimeras develop severe and often lethal chronic GVHD. In these rat-->mouse chimeras, the rat T cells show limited tolerance to host mouse antigens as determined by various parameters including mixed lymphocyte reaction and cytotoxic T lymphocyte assays in vitro, adoptive transfer of T cells to secondary SCID hosts, and the lack of V beta deletion to endogenous host mtv antigens. GVHD in irradiated rat-->SCID chimeras is most prominent with Lewis FL but also applies to Fisher 344 and Wistar Furth FL cells. The failure of newly formed rat T cells in rat-->SCID chimeras to become fully tolerant to host mouse antigens appears to be due to depletion of host antigen-presenting cells by irradiation. Thus, rat-->SCID chimeras generated by transplanting rat FL cells into unirradiated neonatal SCID mice fail to develop GVHD, and the rat T cells display self-tolerance. As allogeneic H-2-different mouse FL-->irradiated SCID chimeras display strong self-tolerance, presumably through recognition of host antigens on thymic epithelial cells, the implication is that mouse thymic epithelial cells are tolerogenic only for mouse and not for rat immature T cells.


This article has been cited by other articles:


Home page
 J. Immunol.Home page
A. Skapenko, G. U. Niedobitek, J. R. Kalden, P. E. Lipsky, and H. Schulze-Koops
Generation and Regulation of Human Th1-Biased Immune Responses In Vivo: A Critical Role for IL-4 and IL-10
J. Immunol., May 15, 2004; 172(10): 6427 - 6434.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1997 by the American Society for Investigative Pathology.