FREQUENCY-ANALYSIS OF CYTOTOXIC T-LYMPHOCYTE PRECURSORS IN SEARCH FORDONORS IN BONE-MARROW TRANSPLANTATION

The usefulness of cytotoxic T lymphocytes precursors (CTLp) frequency analysis in the search for donors in bone marrow transplantation was s tudied. The frequency of anti-recipient CTLp was approached by limitin g dilution assay in HLA matched unrelated, HLA partially matched relat ed and HLA genotypically identical donors. The majority of patients ex amined were affected with different hematological malignancies. Allore active CTLp recognizing non-HLA gene products were not detected in pre transplant examination of two pairs of HLA identical siblings. However , an increased incidence of allospecific CTLp was identified in HLA ma tched MLC negative unrelated pairs. Thus, CTLp assay allowed to uncove r the residual Class I incompatibilities that remained hidden in stand ard serotyping. In two matched unrelated pairs with high pretransplant CTLp frequency the severe acute graft-versus-host disease (GVHD) deve loped after bone marrow transplantation. Examination of other relative s in patients lacking an HLA identical sibling showed the importance o f Class I incompatibility for CTLp generation as well. The lack of cor relation between CTLp frequency and HLA-D disparity could suggest that Class II antigens do not participate in CTLp induction. With one exce ption we had good correlation between MLC and DNA analysis of Class II antigens demonstrating that MLC gives interpretable results even in u nrelated pairs. Our results demonstrate the significance of CTLp frequ ency assay in detection of residual Class I incompatibilities in match ed unrelated pairs and in assessment of Class I compatibility in relat ed pairs. For that it should be used in the final selection of BMT don ors.