The H-2 type of mice has been demonstrated in several different viral systems to play an important role in determining the susceptibility or resistance to MuLV-associated leukemogenesis, and it is clear that the immunologic system of the mouse is the major mediator of this H-2 effect by its influence on the occurrence of an effective immune response to viral and/or tumor antigens. Depending on the virus/host combinations used in various studies, the H-2 effect has proved to map in different subregions of the H-2 complex, suggesting that defective responses on the part of different components of the immune system may be the basis for susceptibility (i.e., defective resistance) in different cases. Having extensively studied the cytotoxic T lymphocyte (CTL) response in H-2-congenic BALB/c mouse strains to syngeneic Friend and Gross virus-induced tumors, we now propose to expand our approach to include the study of helper T lymphocyte and suppressor cell participation in the H-2-associated leukemia resistance phenomenon. Methods to be explored include: transfer of tumor resistance by lymphocyte subsets, generation of helper T lymphocyte responses and study of their participation in the generation of CTL and in antibody production, proliferation experiments with syngeneic tumor cells as stimulators, and diverse experiments designed to explore the possible involvement of T cell suppression in the nonresponsiveness of H-2b/H-2d heterozygotes (by comparison with H-2b homozygotes) to H-2b-homozygous FV tumor cells.
| Ruan, K S; Lilly, F (1992) Approach to a retrovirus vaccine: immunization of mice against Friend virus disease with a replication-defective Friend murine leukemia virus. Proc Natl Acad Sci U S A 89:12202-6 |
| Ruan, K S; Lilly, F (1991) Identification of an epitope encoded in the env gene of Friend murine leukemia virus recognized by anti-Friend virus cytotoxic T lymphocytes. Virology 181:91-100 |
| Polsky, D; Lilly, F (1991) Suppression of H-2b-associated resistance to Friend erythroleukemia virus by a class I gene from the H-2d major histocompatibility complex haplotype. Proc Natl Acad Sci U S A 88:9243-7 |
| Hoatlin, M E; Kozak, S L; Lilly, F et al. (1990) Activation of erythropoietin receptors by Friend viral gp55 and by erythropoietin and down-modulation by the murine Fv-2r resistance gene. Proc Natl Acad Sci U S A 87:9985-9 |
| Holt, C A; Osorio, K; Lilly, F (1986) Friend virus-specific cytotoxic T lymphocytes recognize both gag and env gene-encoded specificities. J Exp Med 164:211-26 |
