Prevention of Graft Versus Host Disease by Inactivation of Host Antigen-Presenting Cells

Author:

Shlomchik Warren D.1,Couzens Matthew S.1,Tang Cheng Bi1,McNiff Jennifer2,Robert Marie E.3,Liu Jinli45,Shlomchik Mark J.45,Emerson Stephen G.16

Affiliation:

1. Department of Medicine, Hematology and Oncology Division,

2. Department of Dermatology,

3. Department of Pathology,

4. Department of Laboratory Medicine,

5. Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.

6. Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Abstract

Graft versus host disease, an alloimmune attack on host tissues mounted by donor T cells, is the most important toxicity of allogeneic bone marrow transplantation. The mechanism by which allogeneic T cells are initially stimulated is unknown. In a murine allogeneic bone marrow transplantation model it was found that, despite the presence of numerous donor antigen-presenting cells, only host-derived antigen-presenting cells initiated graft versus host disease. Thus, strategies for preventing graft versus host disease could be developed that are based on inactivating host antigen-presenting cells. Such strategies could expand the safety and application of allogeneic bone marrow transplantation in treatment of common genetic and neoplastic diseases.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference28 articles.

1. Horowitz M. M., et al., Blood 75, 555 (1990);

2. Gaziev D., et al., Transplantation 63, 854 (1997).

3. Identification of a Graft Versus Host Disease-Associated Human Minor Histocompatibility Antigen

4. Wang W. et al. 269 1588 (1995).

5. N. J. Chao and H. J. Deeg in Graft-Vs.-Host Disease J. L. Ferrara H. J. Deeg S. J. Burakoff Eds. (Dekker New York 1996) pp. 639–666.

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