IDENTIFICATION OF HLA-UNRESTRICTED CD8+ CD28- CYTOTOXIC T-CELL CLONESSPECIFIC FOR LEUKEMIC BLASTS IN CHILDREN WITH ACUTE-LEUKEMIA/

We report on the identification of 57 T-cell clones (TCC) cytolytic to autologous leukemic blasts (LB) but not autologous bone marrow remiss ion cells, LB-reactive TCC were obtained from 3 children with acute le ukemia at remission; all expressed the same phenotype, CD3/ TCR alpha beta/CD8+, but were heterogeneous for the expression of V beta T-cell receptor (TCR) V region chains, thus showing that these cells were not derived from the expansion of a single clone, Cytolytic activity of L B-reactive TCC was not restricted to autologous LB because they were a lso able to lyse phenotypically similar allogeneic LB but not bone mar row remission cells of the same patients. Neither autologous nor allog eneic LB used in the present study as stimulator and target cells expr essed CD80 (B7/BB-1) antigen, and LB-reactive TCC were CD28-. Cytolyti c activity of the clones was only inhibited by anti-CD11a (LFA-1) mAb but not by mAbs specific for HLA class I and II, CD3, CD8, or TCR alph a beta. In conclusion, these data suggest that a subset of apparently HLA-unrestricted, CD3/TCR alpha beta/CD8+ CD28- cytotoxic T lymphocyte s, which use a TCR/CD3-independent recognition pathway, is primarily i nvolved in antitumor immune response of children with acute leukemia a t remission, possibly contributing to the control of minimal residual disease.