Interferon-gamma-based mixed lymphocyte culture as a selection tool for allogeneic bone marrow donors other than identical siblings

Selection procedures in bone marrow transplantation (BMT) would benefit fro m the development of easy-to-perform cellular assays with high discriminati ve power. We tested a cytokine-based mixed lymphocyte culture (MLC) and com pared its outcome to the routinely used MLC, helper T-lymphocyte precursor (HTLp)-f and cytotoxic T-lymphocyte precursor (CTLp)-f assays. Interferon ( IFN)gamma was selected as a marker cytokine for (deleterious) T-helper 1 li ke responses and 36 (potential) BMT donor-recipient pairs were analysed. Th e IFN gamma-MLC appeared sensitive to HLA class II (subtype) differences, b ut not to isolated class I differences, or to mismatches other than HLA (id entical siblings). The test enabled a distinction between combinations with positive MLC (proliferation) and HTLp-f, exemplified by the fact that alth ough high IFN gamma levels were observed in the class IT mismatched group, certain DRB3, DQB l-subtype and DRB1-subtype mismatches did not give rise t o IFN gamma production. This might be of relevance for the detection of so- called permissible mismatches. With regard to prediction of acute graft-ver sus-host disease (aGVHD) in unrelated BMT, the data indicated that high lev els of IFN gamma coincided with severe aGVHD, whereas low levels were large ly associated with grades O-I, However, in the case of isolated class I mis matches the test had no predictive value. The cell-saving IFN gamma-MLC pro vides an alternative for the assays currently in use, but should be employe d along with an assay that is sensitive to class I differences to correct f or false negatives, Consequently, a combination of IFN gamma-MLC and CTLp-f assays seems most promising for donor selection, other than identical sibl ings.