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Effects of anti-CD3 monoclonal antibody on engraftment of T-cell- depleted bone marrow allografts in mice: host T-cell suppression, growth factors, and space

K Hiruma, R Hirsch, M Patchen, JA Bluestone and RE Gress

Experimental Immunology Branch, National Cancer Institute, Bethesda, MD.

To investigate the role of CD3-positive T cells in allogeneic marrow rejection in mice and to examine the effects of anti-CD3 monoclonal antibody (MoAb) on allogeneic marrow engraftment, a hamster MoAb, 145- 2C11, with specificity for the CD3 epsilon portion of the murine T-cell receptor complex was administered to B6 (H-2b) mice that had been sublethally irradiated with 626 cGy and injected with 10 x 10(6) T-cell- depleted B6C3F1 (H-2b/k) bone marrow cells. Lymphoid chimerism status was assessed by flow cytometric analysis of peripheral blood lymphocytes using H-2k-specific MoAb 5 to 6 weeks after bone marrow transplantation. When hosts were treated with 400 micrograms of anti- CD3 MoAb at the time of marrow injection, the percentage of donor-type cells was 75.2% +/- 15.0%, while it was 1.9% +/- 1.2% in untreated mice. It was demonstrated that anti-CD3 MoAb not only suppressed T-cell function but also induced colony-stimulating factors in host mice, and that enhancement of marrow engraftment in anti-CD3 MoAb-treated mice was associated with factor release as well as suppression of host T- cell function. Results were consistent with engraftment being enhanced by a differential response of donor (rather than host) marrow to serum factors in association with host T-cell immunocompromise.

Volume 79, Issue 11, pp. 3050-3058, 06/01/1992
Copyright © 1992 by The American Society of Hematology


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  Copyright © 1992 by American Society of Hematology         Online ISSN: 1528-0020