Characterization of alloimmunization-induced T lymphocytes reactive against AKR leukemia in vitro and correlation with graft-vs-leukemia activity in vivo

• Published in: The Journal of immunology (1950) Vol. 131; no. 4; pp. 2050 - 2058
• Main Authors: Truitt, RL, Shih, CY, Lefever, AV, Tempelis, LD, Andreani, M, Bortin, MM
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01.10.1983; American Association of Immunologists
• Subjects: Animal tumors. Experimental tumors; Animals; Biological and medical sciences; Cytotoxicity, Immunologic; Dose-Response Relationship, Immunologic; Epitopes - analysis; Experimental malignant blood diseases; Graft vs Host Reaction; H-2 Antigens - administration & dosage; Immunologic Memory; Leukemia, Experimental - immunology; Leukemia, Lymphoid - immunology; Lymphocyte Depletion; Lymphocyte Transfusion; Lymphocytes - immunology; Medical sciences; Mice; Mice, Inbred AKR; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred DBA; T-Lymphocytes - classification; T-Lymphocytes - immunology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - transplantation; Tumors; Graft versus leukemia reaction; Effectory cell; Rodentia; Cytotoxicity; Malignant hemopathy; In vitro; In vivo; Vertebrata; Mammalia; Mouse; T-Lymphocyte; Experimental tumor; Alloimmunization
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.131.4.2050

We have reported that immunization of H-2k mice with lymphoid cells from various allogeneic strains induced a population of cells that could eliminate first-passage spontaneous AKR leukemia from the spleens of immuno-suppressed AKR (H-2k) hosts. In the present study, we examined the nature of the cells responsible for this graft-vs-leukemia (GVL) reaction and compared them to cytolytic cells detected in vitro. Spleen cells from alloimmunized CBA/J (H-2k) mice were selectively depleted of various subpopulations by treatment with antibody and complement (C), then tested in vivo for GVL reactivity. Cell suspensions depleted of Thy-1.2+, Lyt-1+, or Lyt-2+ lymphocytes had no significant GVL reactivity, whereas suspensions depleted of NK-1.2+ cells retained GVL reactivity. The GVL-reactive cells persisted in H-2-compatible donor mice for up to 56 days. Lyt-1+2+ lymphocytes that were cytotoxic for cultured AKR leukemia cells in vitro could be detected in the spleens of alloimmunized H-2-compatible mice after expansion of the cells in T cell growth factor. Using quantitative limiting dilution cytotoxicity assays, we found that the frequency of leukemia-reactive cytotoxic lymphocytes (CL) in the spleen showed a direct correlation with the GVL efficacy of the cells in vivo. Alloimmunization was essential for induction of the GVL-reactive cell population. CL in alloimmunized mice consisted of heterogeneous cytotoxic specificities; i.e., some CL were leukemia-specific, others lysed only nonleukemic AKR target cells, and a third group mediated killing of both leukemic and nonleukemic target cells. The CL appeared to be H-2 restricted and specific for non-H-2 antigens shared by the AKR leukemia and the alloimmunizing cells.