Comparison of helper and cytotoxic antirecipient T cell frequencies in unrelated bone marrow transplantation

Abstract

Donor/recipient histocompatibility antigen differences initiate acute graft-versus-host disease (GVHD) after bone marrow transplantation. Frequency 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 predictor for the development of moderate-to-severe acute GVHD. Here, we describe a sensitive assay for measuring alloreactive helper (IL-2-producing) T lymphocyte precursor (HTLp) frequencies, and compare the ability of this assay and the cytotoxic T lymphocyte precursor (CTLp) assay to detect HLA- class II and class I differences and to predict clinical outcome in a cohort of unrelated donor/recipient BMT pairs. Twenty-two pairs underwent unrelated donor BMT. Patients with high (> 1:100 x 10(3)) HTLp or CTLp frequencies had a higher incidence of moderate-to-severe (grades II-IV) acute GVHD (80% and 100%, respectively) than pairs with low (< 1:100 x 10(3)) frequencies (40% and 57%, respectively). Ten (45%) patients have died, but all patients with both a low HTLp and low CTLp frequency remain alive. The HTLp and CTLp assays provided similar predictive information for outcome. Given that the HTLp assay is more rapid and less labor intensive, it offers an additional or alternative functional method for donor selection in unrelated donor BMT.