摘要 |
Patients who develop increased numbers of gammadelta+ cytotoxic T lymphocytes 2-6 months after allogeneic bone marrow transplantation are less likely to relapse than those who do not. The gammadelta+ T cells isolated from blood of patients with increased gammadelta+ T cells are CD3+CD4-CD8-CD57+, cytolytic to K562 cells, and express the Vdelta1 T cell receptor phenotype. Similar gammadelta+ T cells can be generated in vitro by culture of donor mononuclear cells which are enriched for gammadelta+ T cells by immunomagnetic depletion of depleted of CD4+ and CD8+ cells. This gammadelta-enriched cell preparation was cultured on a combination of immobilized pan-delta monoclonal antibody and irradiated recipient B cell leukemia. After four weeks, the cultures were almost exclusively Vdelta1+ CD3+CD4-CD8- cells that co-expressed activation-associated antigens CD69, CD25, and HLA-DR. Furthermore, they were cytolytic against the primary leukemia obtained from the recipient and lymphoblastic leukemia cell lines, yet had minimal cytotoxicity against normal donor-derived mononuclear cells or myeloid leulemia cell lines. These observations suggest that donor-derived cytotoxic gammadelta+ T cells can be generated in vitro, and may provide therapeutic potential for prevention of disease relapse.
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