|
|
 Previous Article | Table of Contents | Next Article 
Mechanism for cotolerance in nonlethally conditioned mixed chimeras:
negative selection of the Vbeta T-cell receptor repertoire by both host and
donor bone marrow-derived cells
YL Colson, J Lange, K Fowler and ST Ildstad
Department of Surgery, Division of Cellular Therapeutics, University of
Pittsburgh, PA 15261, USA.
Bone marrow (BM) chimeras prepared by complete recipient ablation (A--
>B) exhibit donor-specific tolerance, yet survival is often limited by
graft-versus-host disease (GVHD). Negative selection of potentially
donor-reactive T cells, as assessed by relative T-cell receptor (TCR)-
Vbeta expression, is dependent on donor BM-derived deleting ligands. Mixed
chimerism and tolerance for both donor and host antigens can be achieved
using partial recipient myeloablation with 500 cGy total-body irradiation
(TBI) before transplantation followed by cyclophosphamide (CyP) on day +2.
To examine the influence of residual host elements on negative selection,
the peripheral TCR-Vbeta repertoire was analyzed in partially ablated
C57BL/10SnJ (B10) recipients reconstituted with BM from major
histocompatibility complex (MHC)-disparate B10.BR/SgSnJ or MHC, Hh-1 and
Mls-disparate BALB/cByJ donors, which delete Vbeta5+ and 11+ or Vbeta3+,
5+, and 11+ TCR subsets, respectively. As in myeloblated recipients,
donor-reactive subfamilies were deleted in B10.BR-->B10 and
BALB/c-->B10 chimeras, suggesting that donor I-E and minor
lymphocyte-stimulating (Mls) antigens contribute to the deleting ligands in
the nonmyeloablated host. In striking contrast to completely ablated
B10-->B10.BR chimeras, partially ablated recipients showed
intramedullary I-E expression in the thymus and deleted host-reactive
Vbeta5+ and Vbeta11+ subfamilies. These data demonstrate that efficient
clonal deletion occurs after partial myeloablation and that both donor and
host ligands contribute to TCR repertoire selection.
Volume 88,
Issue 12,
pp. 4601-4610,
12/15/1996
Copyright © 1996 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
R. Chakraverty, H.-S. Eom, J. Sachs, J. Buchli, P. Cotter, R. Hsu, G. Zhao, and M. Sykes
Host MHC class II+ antigen-presenting cells and CD4 cells are required for CD8-mediated graft-versus-leukemia responses following delayed donor leukocyte infusions
Blood,
September 15, 2006;
108(6):
2106 - 2113.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Xu, P. M. Chilton, Y. Huang, C. L. Schanie, and S. T. Ildstad
Production of Donor T Cells Is Critical for Induction of Donor-Specific Tolerance and Maintenance of Chimerism
J. Immunol.,
February 1, 2004;
172(3):
1463 - 1471.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Mielcarek, P. J. Martin, W. Leisenring, M. E. D. Flowers, D. G. Maloney, B. M. Sandmaier, M. B. Maris, and R. Storb
Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation
Blood,
July 15, 2003;
102(2):
756 - 762.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
