Humanized or chimeric
monoclonal antibodies (MoAbs) directed against the
interleukin-2 (IL-2) receptor alpha-chain, CD25, are promising
immunosuppressive agents due to improved pharmacokinetic profiles and less toxicity. These MoAbs have been used effectively in preventing and/or treating rejection in solid
organ transplantation and are currently under investigation for prevention/treatment of
graft-versus-host disease (GvHD) in
stem cell transplantation. We analysed the in vitro activities of the chimeric anti-CD25 MoAb
basiliximab and the humanized anti-CD25 MoAb
daclizumab in various test systems for alloimmune response and T cell activation in comparison to
cyclosporin A (CsA) and
prednisolone. Anti-CD3- and
alloantigen-induced T cell proliferation were decreased significantly by the anti-CD25 MoAbs in a dose-dependent fashion. At a concentration of 10 ng/ml
daclizumab and CsA synergistically decreased T cell proliferation of mixed lymphocyte cultures, whereas
basiliximab showed only subadditive activity. Simultaneous addition of the anti-CD25 MoAbs and
prednisolone did not result in combined activity. Addition of exogenous
IL-2 completely overcame the inhibitory effect on T cell proliferation of both anti-CD25 MoAbs, but not that of CsA and
prednisolone. Anti-CD25 MoAbs inhibited the generation of
antigen-specific cytotoxic T lymphocytes in a limiting dilution assay, whereas they showed no effect on the cytolytic activity of established
antigen-specific T cell clones. This in vitro study demonstrates strong immunosuppressive activity by both chimeric and humanized MoAbs against CD25. The combined activity with CsA justifies their early use for prevention rather than treatment of GvHD.