Depletion of alloreactive T cells by a specific anti-interleukin-2 receptor p55 chain immunotoxin does not impair in vitro antileukemia and antiviralactivity

The success of bone marrow transplantation (BMT) from HLA-disparate donors depends on the development of new strategies able, on one hand, to efficien tly prevent graft-versus-host disease (GVHD) and, on the other hand, to pro tect leukemic patients from relapse and infections. Using an immunotoxin (I T) directed against the alpha chain (p55) of the human interleukin-2 recept or (RFT5-SMPT-dgA), we previously showed that it is possible to kill mature T cells activated against a specific HLA complex by a one-way mixed lympho cyte culture (MLC). The present study was performed to investigate whether this protocol of allodepletion affects the capacity of residual T cells to display antileukemia and antiviral activity evaluated by limiting dilution assays (LDA), measuring the frequency of cytotoxic T-lymphocyte precursors (CTLp) directed against autologous leukemic blasts (LB) and cytomegalovirus (CMV)- and Epstein-Barr virus (EBV)-infected target cells. Antileukemia ac tivity was evaluated in peripheral blood mononuclear cells (PBMC) of 3 pati ents treated for acute myeloid leukemia who had developed a high frequency of LB-reactive CTLp after either autologous or allogeneic BMT. Results demo nstrate that (1) depletion with RFT5-SMPT-dgA efficiently inhibited MLC; (2 ) fresh PBMC of patients yielded a high frequency of LB-reactive CTLp compa rable to that of the mock-treated PBMC; and (3) effector cells obtained aft er allodepletion fully retained the capacity to lyse pretransplant LB, By c ontrast, the frequency of CTLp directed against patient's pretransplant BM remission cells was always undetectable. Data obtained in 4 healthy donors showed that specifically allodepleted T cells recognized and killed autolog ous CMV-infected fibroblasts and autologous EBV-B lymphoblastoid cell lines . In conclusion, our data Indicate that allodepletion using RFT5-SMPT-dgA e fficiently removed alloreactive cells, while sparing in vitro antileukemic and antiviral cytotoxic responses, (C) 1999 by The American Society of Hema tology.