Cytotoxic T cell activity after HLA-mismatch bone marrow transplantation

Six patients with various hematologic diseases were treated with HLA-haploidentical bone marrow mismatched for 1-2 loci at the disparate chromosome with a relative response in the mixed lymphocyte reaction (MLR) ranging between 0.04 and 0.96 (median 0.27). Thirty to 371 days after bone marrow grafting, patient lymphocytes (of donor origin) were tested for reactivity in mixed lymphocyte culture (MLC) and cell mediated lympholysis (CMLy) to lymphocytes from the host (cryopreserved before grafting), the marrow donor, and unrelated individuals. After grafting, Lymphocytes from the patients showed a host-specific decrease in proliferation and in cytotoxic response (%51Cr release in a standard chromium release assay), when compared to the pretransplant host-specific donor response, whereas the responses towards third party cells were unaffected. This host-specific unresponsiveness after HLA-mismatch bone marrow transplantation is compatible with a clonal deletion theory and might be the reason that this procedure is at all possible.