COMPARISON OF HELPER AND CYTOTOXIC ANTIRECIPIENT T-CELL FREQUENCIES IN UNRELATED BONE-MARROW TRANSPLANTATION

Donor/recipient histocompatibility antigen differences initiate acute graft versus-host disease (GVHD) after bone marrow transplantation. Fr equency analysis, using limiting dilution techniques, of functionally defined (helper or cytotoxic) antirecipient T lymphocyte precursors in the peripheral blood of the donor has been shown to be an accurate pr edictor for the development of moderate-to-severe acute GVHD. Here, we describe a sensitive assay for measuring alloreactive helper (IL-2-pr oducing) T lymphocyte precursor (HTLp) frequencies, and compare the ab ility of this assay and the cytotoxic T lymphocyte precursor (CTLp) as say to detect HLA- class II and class I differences and to predict cli nical outcome in a cohort of unrelated donor/recipient BMT pairs. Twen ty-two pairs underwent unrelated donor BMT. Patients with high (>1:100 x10(3)) HTLp or CTLp frequencies had a higher incidence of moderate-to -severe (grades II-IV) acute GVHD (80% and 100%, respectively) than pa irs with low (<1:100x10(3)) frequencies (40% and 57%, respectively). T en (45%) patients have died, but all patients with both a low HTLp and low CTLp frequency remain alive. The HTLp and CTLp assays provided si milar predictive information for outcome. Given that the HTLp assay is more rapid and less labor intensive, it offers an additional or alter native functional method for donor selection in unrelated donor BMT.