Identification of HLA-unrestricted CD8+/CD28- cytotoxic T-cell clones specific 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 remission cells. LB-reactive TCC were obtained from 3 children with acute leukemia 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 LB-reactive TCC was not restricted to autologous LB because they were also able to lyse phenotypically similar allogeneic LB but not bone marrow remission cells of the same patients. Neither autologous nor allogeneic LB used in the present study as stimulator and target cells expressed CD80 (B7/BB-1) antigen, and LB-reactive TCC were CD28-. Cytolytic 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 alpha beta. In conclusion, these data suggest that a subset of apparently HLA-unrestricted, CD3/TCR alpha beta/CD8+ CD28- cytotoxic T lymphocytes, which use a TCR/CD3-independent recognition pathway, is primarily involved in antitumor immune response of children with acute leukemia at remission, possibly contributing to the control of minimal residual disease.
Montagna
D
D
Department of Pediatrics, University of Pavia, IRCCS Policlinico San Matteo, Italy.
Aricò
M
M
Montini
E
E
De Benedetti
F
F
Maccario
R
R
D000911:Antibodies, Monoclonal / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D018106:CD28 Antigens; D002648:Child; D006801:Humans; D016130:Immunophenotyping / Q000379:methods*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens