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

Abstract

To investigate the role of CDS-positlve 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∈ 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 × 106 T-cell-depleted B6C3F1 (H-2b/k) bone marrow cells. Lympoid 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 μg 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. This is a US government work. There are no restrictions on its use.