Antigen-specific recognition of autologous leukemia cells and allogeneic class-I MHC antigens by IL-2-activated cytotoxic T cells from a patient with acute T-cell leukemia.
Culturing of leukemic blood lymphocytes from a patient with acute T-cell lymphoblastic leukemia (T-ALL) with interleukin-2 (IL-2) yielded T-cell line AK-1 with a remarkable cytotoxic specificity. This line mediated strong lysis of tumor target lines expressing major histocompatibility complex (MHC) class I antigens, such as Raji, CEM, and Molt-4 cells, but no killing of K562 and Daudi cells, which are deficient in MHC class I. In contrast, lymphokine-activated killer (LAK) cells from normal donors destroyed all these tumor targets, without MHC restriction. Line AK-1, originating from residual normal T cells present in the leukemic blood, lysed autologous leukemic blasts and peripheral blood lymphocytes (PBL) from many but not all allogeneic individuals but failed to kill autologous remission lymphocytes. Destruction of the autologous leukemic targets by AK-1 could be inhibited by unlabeled competitor target cells that were lysed by AK-1, but not by target cells that were not lysed. This suggests that AK-1 specifically recognized an alien determinant on the autologous ALL cells, crossreactive with allogeneic MHC class I antigens. This reactivity with some degree of tumor specificity may be a leukemic equivalent to responses reported for populations of tumor infiltrating lymphocytes (TIL) seen in some solid tumors.
Fisch
P
P
Department of Human Oncology, University of Wisconsin, Madison 53792.
Weil-Hillman
G
G
Uppenkamp
M
M
Hank
J A
JA
Chen
B P
BP
Sosman
J A
JA
Bridges
A
A
Colamonici
O R
OR
Sondel
P M
PM
D000328:Adult; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D017252:CD3 Complex; D003602:Cytotoxicity, Immunologic; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta