RELATIVE ROLES OF NATURAL-KILLER-CELL-MEDIATED AND T-CELL-MEDIATED ANTILEUKEMIA EFFECTS IN CHRONIC MYELOGENOUS LEUKEMIA PATIENTS TREATED WITH INTERFERON-ALPHA

Potential anti-leukemia effects mediated by T cells or by natural kill er (NK) cells were investigated in chronic myelogenous leukemia (CML) patients treated with interferon-alpha. Therapy-associated modulation of T cell and NK reactivity was monitored for one year from initiation in autologous mixed lymphocyte-tumor cell reactions and cytotoxicity directed against autologous CML cells, respectively. During the course of IFN-therapy, NK activity against autologous CML cells increased st eadily, whereas T cell reactivity fluctuated randomly. Despite the hig h level of T cell reactivity to autologous tumor cells in short-term ( 6 days) culture, 1) they failed to respond to synthetic peptides corre sponding to the bcr/abl fusion sequence of the patient, and 2) only on e proliferative T cell clone (TCC) was isolated which specifically rec ognized HLA-DR-matched CML cells. This TCC appeared not to recognize s ynthetic peptides corresponding to the bcr/abl fusion sequence of the patient; the antigen to which it responds remains unknown. To assess p otential immunogenicity of bcr/abl peptides, it was attempted to sensi tize T cells from normal donors in vitro. Of 109 cell lines obtained f rom seven different donors, eleven showed peptide-dependent proliferat ion. Therefore, although these results show that it is possible to iso late apparently CML-specific T cells from patients, as well as to prim e T cells against tumor-specific peptide in vitro, the frequency of su ch T cell-mediated reactivity appears low and its relevance to anti-le ukemic effects questionable. On the other hand, the strong time-depend ent enhancement of natural killing of autologous CML blasts during IFN -alpha treatment, a phenomenon not observed for T cell reactivity, sug gests that natural immunity may be more important in controlling disea se.