The Journal of Immunology, Vol 141, Issue 7 2282-2288, Copyright © 1988 by American Association of Immunologists

ARTICLES

Effects of T cell depletion in radiation bone marrow chimeras. I. Evidence for a donor cell population which increases allogeneic chimerism but which lacks the potential to produce GVHD

M Sykes, M Sheard and DH Sachs
Transplantation Biology Section, National Cancer Institute, Bethesda, MD 20892.

The opposing problems of graft-vs-host disease (GVHD) and failure of alloengraftment present major obstacles to the application of bone marrow transplantation (BMT) across complete MHC barriers. The addition of syngeneic T-cell-depleted (TCD) bone marrow (BM) to untreated fully allogeneic marrow inocula in lethally irradiated mice has been previously shown to provide protection from GVHD. We have used this model to study the effects of allogeneic T cells on levels of chimerism in recipients of mixed marrow inocula. The results indicate that T cells in allogeneic BM inocula eliminate both coadministered recipient- strain and radioresistant host hematopoietic elements to produce complete allogeneic chimerism without clinical GVHD. To determine the role of GVH reactivity in this phenomenon, we performed similar studies in an F1 into parent combination, in which the genetic potential for GVHD is lacking. The presence of T cells in F1 marrow inocula led to predominant repopulation with F1 lymphocytes in such chimeras, even when coadministered with TCD-recipient-strain BM. These results imply that the ability of allogeneic BM cells removed by T cell depletion to increase levels of allochimerism may be mediated by a population which is distinct from that which produces GVHD. These results may have implications for clinical BM transplantation.

This article has been cited by other articles:

				J. Bagley, M. L. Cortes, X. O. Breakefield, and J. Iacomini Bone marrow transplantation restores immune system function and prevents lymphoma in Atm-deficient mice Blood, July 15, 2004; 104(2): 572 - 578. [Abstract] [Full Text] [PDF]

				Y.-M. Kim, M. Y. Mapara, J. D. Down, K. W. Johnson, F. Boisgerault, Y. Akiyama, G. Benichou, M. Pelot, G. Zhao, and M. Sykes Graft-versus-host-reactive donor CD4 cells can induce T cell-mediated rejection of the donor marrow in mixed allogeneic chimeras prepared with nonmyeloablative conditioning Blood, January 15, 2004; 103(2): 732 - 739. [Abstract] [Full Text] [PDF]

				S. Saijo, M. Kotani, K. Habu, C. Ishitsuka, H. Yamamoto, T. Sekiguchi, and Y. Iwakura Bone Marrow-Derived Cells Are Responsible for the Development of Autoimmune Arthritis in Human T Cell Leukemia Virus Type I-Transgenic Mice and Those of Normal Mice Can Suppress the Disease J. Immunol., November 15, 1999; 163(10): 5700 - 5707. [Abstract] [Full Text] [PDF]

				Y.-G. Yang, J. J. Sergio, D. A. Pearson, G. L. Szot, A. Shimizu, and M. Sykes Interleukin-12 Preserves the Graft-Versus-Leukemia Effect of Allogeneic CD8 T Cells While Inhibiting CD4-Dependent Graft-Versus-Host Disease in Mice Blood, December 1, 1997; 90(11): 4651 - 4660. [Abstract] [Full Text] [PDF]