Mouse leukemia and solid tumors treated with bone marrow grafting.

Mice of the AKR strain are characterised by a high incidence of spontaneous thymic lymphomas. AKR chromosomes contain the genomes of ecotropic murine leukaemia virus (MuLV) at two loci, termed Akv-1 and Akv-2 (refs 2-6). Shortly after birth, the normal tissues of AKR mice begin to produce high levels of this XC-positive MuLV (ref. 7) (that is, one that forms XC plaques). A second class of MuLV, termed mink cell focus-inducing virus (MCF), is produced specifically by preleukaemic and leukaemic AKR thymocytes. Nowinski et al. have established a series of tissue culture lines from AKR leukaemias and reported that the resulting cell lines produce virus particles, but that these particles, surprisingly, do not give rise to XC plaques. We have analysed the virus particles produced by one of these cell lines, termed AKRSL2. We show here that, unlike most or all of the nonmalignant tissues in the AKR mouse, these cultured lymphoma cells produce very little non-defective ecotropic MuLV; however, they do produce replication-defective ecotropic MuLV.

AKR murine leukemia virus↗

PubMed1979

Viral specificity of H-2-restricted T killer cells directed against syngeneic tumors induced by Gross, Friend, or Rauscher leukemia virus.

Cytolytic T lymphocytes (CTL) were generated against murine tumors induced by Gross, Friend, or Rauscher leukemia virus (LV) in syngeneic mixed leukocyte-tumor cell cultures. Analogous to the patterns of specificity observed with antibodies to LV-induced cell surface antigens, CTL could be classified into two major groups of specificity. Tumor cells induced by Friend, Moloney, or Rauscher virus and positive for the FMR antigen were killed by syngeneic CTL immune to any one of these three LV; the same CTL, however, were incapable of killing syngeneic tumor cells induced by Gross LV. The converse was true for Gross LV-specific CTL: these CTL were specific for syngeneic tumor cells expressing the Gross virus-associated cell-surface antigen (GCSA), and not the FMR antigen. The H-2 specificities of the two groups of LV-immune CTL were also compared, because in both cases, CTL were restricted in their killing activity to H-2-identical tumor target cells. When CTL from single strains of mice were generated against syngeneic FMR- or GCSA-positive tumor cells, differences were observed with respect both to the requirement for the expression of compatible H-2K or H-2D specificities, and to the intensity of the CTL response in congenic mice of the H-2b, H-2d, and H-2k haplotypes.

AKR murine leukemia virus↗

PubMed1979

The generation and specificity of cytotoxic T cells raised against syngeneic tumor cells bearing AKR/Gross murine leukemia virus antigens.

Efforts were made to generate C57BL/6 cytotoxic effector cells to a syngeneic leukemia (E{male}G2) bearing AKR/Gross virus antigens. As we were unable to induce significant cytotoxic activity by immunization with up to 10(8) irradiated E{male}G2 cells, even when cells from such primed animals were subsequently restimulated with E{male}G2 cells in vitro, C57BL/6 mice were immunized with an aliogeneic, virus-producing AKR leukemic cell line (AKR SL3). Peritoneal exudate cells and, to a lesser degree, spleen cells from these mice showed significant lytic activity toward the immunizing allogeneic tumor but not toward E{male}G2. When spleen cells were harvested from animals {approximately equal to}10 d after injection of AKR SL3 and rechallenged in vitro with either E{male}G2 or AKR.H-2(b) SL1, another tumor that displays AKR/Gross virus antigens, then a vigorous cytotoxic response against E{male}G2 and AKR. H-2(b) SL1 was obtained. Effector cells generated by AKR SL3 priming followed by in vitro stimulation with E{male}G2 or AKR.H-2(b) SL1 lysed only cells of H-2(b) haplotype which were strongly positive for the display of serologically detectable AKR/Gross virus antigens. Thus, AKR SL3 cells were not lysed nor were EL4 cells (H-2(b); but only weakly positive for gp70). Cells not bearing the MuLV antigens tested for, such as P815 mastocytoma cells and spleen cell "blasts" from C57BL/6 and CBA (H-2(k)) mice, were also insusceptible to attack. The cytotoxic effector cells induced bore Thy 1.2 alloantigen and were of the Lyt 1+2+ phenotype. Collectively, these findings are consistent with the conclusion that the cytotoxic T cells raised against E{male}G2 are directed against AKR/Gross virus-associated antigens and are H-2 restricted. It will be of interest to determine the relevance of such effector cells to the known resistance of the C57BL/6 mouse to AKR/Gross virus-induced leukemia.

AKR murine leukemia virus↗