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.
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.
Hiruma
K
K
Experimental Immunology Branch, National Cancer Institute, Bethesda, MD.
Hirsch
R
R
Patchen
M
M
Bluestone
J A
JA
Gress
R E
RE
D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D016026:Bone Marrow Transplantation; D017252:CD3 Complex; D003115:Colony-Stimulating Factors / Q000378:metabolism; D005434:Flow Cytometry; D006084:Graft Rejection; D006183:H-2 Antigens / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003115:Colony-Stimulating Factors; D006183:H-2 Antigens; D011948:Receptors, Antigen, T-Cell