FREQUENCY OF BONE-MARROW T-CELLS RESPONDING TO HLA-IDENTICAL NONLEUKEMIC AND LEUKEMIC STIMULATOR CELLS

Grafted immunocompetent cells are considered responsible for GVHD as w ell as for the elimination of residual leukemic cells ('graft-versus-l eukemia reactivity', GVLR) in leukemic patients after allogeneic BMT. Clinical and experimental investigations have given contradictory answ ers to the question whether GVHD and GVLR are two manifestations of th e same process or separate immunologic processes. We have addressed th is question by analysing the primary in vitro response of BM-derived p roliferating and cytotoxic T lymphocyte precursors (PTLp and CTLp) in HLA identical relative pairs (n = 17). PTLp frequency estimation revea ls strong responses (> 1 in 5000) on non-leukemic as well as leukemic stimulation in a majority of cases. CTLp amount variably to 10-100% of the proliferating precursor cells. Preliminary specificity analyses s how that on non-leukemic stimulation about 90% of colonies exhibit exc lusive lysis of the non-leukemic target. At the same time, on leukemic stimulation, about 75% of cytolytic colonies are exclusively reactive against leukemic targets without crossreactivity against nonleukemic targets from the same patient. Our data show that primary in vitro res ponses in HLA identical sibling pairs may be as strong as those agains t allo MHC antigens. In addition CTL specifically lysing leukemic or n on-leukemic targets may represent an in vitro model of the immunologic non-identity of GVHD and GVLR.