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Induction of stable chimerism and elimination of graft-versus-host disease by depletion of T lymphocytes from bone marrow using immunomagnetic beads

Hoffman, AL and Makowka, L and Cramer, DV and Cai, X and Banner, B and Pascualone, A and Hoffmann, S and Starzl, TE (1989) Induction of stable chimerism and elimination of graft-versus-host disease by depletion of T lymphocytes from bone marrow using immunomagnetic beads. Surgery, 106 (2). 354 - 363. ISSN 0039-6060

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Abstract

The goal of transplantation is the induction of immunologic tolerance. At present, nonspecific immunosuppression is used to prevent graft rejection and, commonly, graft-versus-host disease (GVHD). Nevertheless, nonspecific immunosuppressive therapy is frequently complicated by infection, malignant tumors, and drug toxicity. In order to examine whether hematopoietic chimerism can be used to induce specific allograft tolerance, we have reconstituted lethally irradiated Lewis rats with ACI bone marrow that has been depleted of T cells with use of immunomagnetic beads. This technique consists of binding OX-19, a mouse anti-rat pan- T lymphocyte monoclonal antibody, to magnetic polymer beads. Mixing of bone marrow or splenocytes with the bead/OX-19 complexes, followed by magnetic separation, results in significant depletion of T cells with minimal nonspecific cell loss. Immunomagnetic T-cell depletion of bone marrow, followed by reconstitution of a lethally irradiated host, allows for the development of stable, mixed hematopoietic chimerae without evidence of GVHD. These hosts are immunocompetent by clinical criteria. Recipients of untreated donor bone marrow that did or did not receive nonspecific immunosuppression demonstrated varying degrees of GVHD and reduced survival. The ability to rapidly and simply deplete T lymphocytes from bone marrow and produce stable, immunocompetent hematopoietic chimerae without GVHD may be an important method for tolerance induction to vascularized allografts. © 1989.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Hoffman, AL
Makowka, L
Cramer, DV
Cai, X
Banner, B
Pascualone, A
Hoffmann, S
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1989
Date Type: Publication
Journal or Publication Title: Surgery
Volume: 106
Number: 2
Page Range: 354 - 363
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0039-6060
Other ID: uls-drl:31735062121987, Starzl CV No. 970
Date Deposited: 08 Apr 2010 17:16
Last Modified: 13 Oct 2017 23:55
URI: http://d-scholarship.pitt.edu/id/eprint/4356

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