Faculty Collaboration Database

Characterization of alloimmunization-induced T lymphocytes reactive against AKR leukemia in vitro and correlation with graft-vs-leukemia activity in vivo. J Immunol 1983 Oct;131(4):2050-8

Date

10/01/1983

Pubmed ID

6194224

Scopus ID

2-s2.0-0020553787 (requires institutional sign-in at Scopus site)   76 Citations

Abstract

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.

Author List

Truitt RL, Shih CY, Lefever AV, Tempelis LD, Andreani M, Bortin MM

MESH terms used to index this publication - Major topics in bold

Animals
Cytotoxicity, Immunologic
Dose-Response Relationship, Immunologic
Epitopes
Graft vs Host Reaction
H-2 Antigens
Immunologic Memory
Leukemia, Experimental
Leukemia, Lymphoid
Lymphocyte Depletion
Lymphocyte Transfusion
Lymphocytes
Mice
Mice, Inbred AKR
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Inbred DBA
T-Lymphocytes
T-Lymphocytes, Cytotoxic