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