The Journal of Immunology, Vol 144, Issue 9 3417-3423, Copyright © 1990 by American Association of Immunologists
Selective elimination in vitro of alloresponsive T cells to human transplantation antigens by toxin or radionuclide conjugated anti-IL-2 receptor (Tac) monoclonal antibody
RW Kozak, DP Fitzgerald, RW Atcher, CK Goldman, DL Nelson, OA Gansow, I Pastan and TA Waldmann
Division of Cytokine Biology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892.
The human allogeneic mixed lymphocyte reaction is the in vitro correlate of
graft rejection. Cytotoxic effector cells generated during an allogeneic
mixed lymphocyte reaction were previously shown to express the human p55
IL-2 receptor subunit, whereas resting cells do not express this receptor
peptide. In this study, we asked whether Pseudomonas exotoxin or
bismuth-212 (an alpha-particle emitting radionuclide) coupled to the
anti-IL-2 receptor mAb, anti-Tac, were able to selectively eliminate
alloresponsive cells generated during an allogeneic mixed lymphocyte
reaction. After assembly, anti-Tac immunoconjugates retained their binding
integrity, specificity, and selectivity. Deletion of alloresponsive cells
was shown by the removal of alloproliferating cells as assessed by
quantitating cell recovery and by measurement of thymidine incorporation
into newly synthesized DNA. Both toxin and radionuclide immunoconjugates
eliminated established cytotoxic effector cells generated in an allogeneic
mixed lymphocyte reaction, while leaving intact the PHA-inducible mitogenic
response of the nonactivated cells. The addition of excess anti-Tac blocked
all of the effects of these cytotoxic reagents. The therapeutic reagents in
vitro were most effective when added just prior to the peak of the
alloproliferative response, when receptor expression would be close to
maximum. Thus, anti-Tac conjugated either with toxin or radionuclide is
effective in vitro in specifically eliminating cytotoxic effector cells.
