Abstract
Resistance to neoplasia caused by radiation-induced leukemia virus (RadLV) is mediated by gene(s) in the H-2D region of the major histocompatibility complex. The previous observation that rapid increases in cellular synthesis and cell-surface expression of H-2 antigens are detectable immediately after virus inoculation has suggested that altered expression of H-2 antigens may play a significant role in the mechanism(s) of host defense to virus infection. This concept is supported by the following observations. First, cell-mediated immunity against RadLV transformed or infected cells can be detected with ease when H-2-positive target cells are used in the cell-mediated lympholysis (CML) assay. (Although RadLV transformed cells obtained from overtly leukemic animals and maintained in tissue culture are H-2 negative, these cells can regain their H-2 phenotype by in vivo passage in normal animals. The H-2-negative cells are poor targets in a CML assay.) Second, resistant mice develop greater numbers of effectors when infected with RadLV than do susceptible mice. Third, injection of normal (uninfected) thymocytes into syngeneic recipients of resistant or susceptible H-2 type does not stimulate a CML response. However, injection of RadLV infected thymocytes from resistant mice produces a vigorous CMI response, and such thymocytes elicit the strongest response at a time when both H-2 and viral antigen expression is elevated. By contrast, injection of infected thymocytes from susceptible mice, which express viral antigens, but low levels of H-2 antigens, does not stimulate a CML reaction. These findings may explain the easier induction of leukemia found by many investigators when virus is inoculated into neonatal mice and the preferential thymus tropism of some oncogenic type-C RNA virus. Cells expressing very low levels of H-2, such as thymocytes, may serve as permissive targets for virus infection because they lack an important component (H-2 antigens) of the dual or altered recognition signal required to trigger a defensive host immune response.
Full Text
The Full Text of this article is available as a PDF (718.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bean M. A., Kodera Y., Cummings K. B., Bloom B. R. Occurrence of restricted suppressor T-cell activity in man. J Exp Med. 1977 Nov 1;146(5):1455–1460. doi: 10.1084/jem.146.5.1455. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boyse E. A., Stockert E., Old L. J. Isoantigens of the H-2 and Tla loci of the mouse: interactions affecting their representation on thymocytes. J Exp Med. 1968 Jul 1;128(1):85–95. doi: 10.1084/jem.128.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boyse E. A., Stockert E., Old L. J. Modification of the antigenic structure of the cell membrane by thymus-leukemia (TL) antibody. Proc Natl Acad Sci U S A. 1967 Sep;58(3):954–957. doi: 10.1073/pnas.58.3.954. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chazan R., Haran-Ghera N. The role of thymus subpopulations in "T" leukemia development. Cell Immunol. 1976 May;23(2):356–375. doi: 10.1016/0008-8749(76)90200-8. [DOI] [PubMed] [Google Scholar]
- Dennert G., Hyman R. The importance of serologically detectable histocompatibility antigens in the induction and effector step of cell-mediated lysis. Eur J Immunol. 1977 May;7(5):251–257. doi: 10.1002/eji.1830070502. [DOI] [PubMed] [Google Scholar]
- Doherty P. C., Blanden R. V., Zinkernagel R. M. Specificity of virus-immune effector T cells for H-2K or H-2D compatible interactions: implications for H-antigen diversity. Transplant Rev. 1976;29:89–124. doi: 10.1111/j.1600-065x.1976.tb00198.x. [DOI] [PubMed] [Google Scholar]
- Forman J., Vitetta E. S. Absence of H-2 antigens capable of reacting with cytotoxic T cells on a teratoma line expressing a T/t locus antigen. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3661–3665. doi: 10.1073/pnas.72.9.3661. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Freedman H. A., Lilly F., Strand M., August J. T. Variations in viral gene expression in Friend virus-transformed cell lines congenic with respect to the H-2 locus. Cell. 1978 Jan;13(1):33–40. doi: 10.1016/0092-8674(78)90135-6. [DOI] [PubMed] [Google Scholar]
- Jones P. P. Analysis of H-2 and Ia molecules by two-dimensional gel electrophoresis. J Exp Med. 1977 Nov 1;146(5):1261–1279. doi: 10.1084/jem.146.5.1261. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LIEBERMAN M., KAPLAN H. S. Leukemogenic activity of filtrates from radiation-induced lymphoid tumors of mice. Science. 1959 Aug 14;130(3372):387–388. doi: 10.1126/science.130.3372.387. [DOI] [PubMed] [Google Scholar]
- Meruelo D., Deak B., McDevitt H. O. Genetic control of cell-mediated responsiveness to an AKR tumor-associated antigen: mapping of the locus involved to the I region of the H-2 complex. J Exp Med. 1977 Nov 1;146(5):1367–1379. doi: 10.1084/jem.146.5.1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meruelo D., Leiberman M., Ginzton N., Deak B., McDevitt H. O. Genetic control of radiation leukemia virus-induced tumorigenesis. I. Role of the major murine histocompatibility complex, H-2. J Exp Med. 1977 Oct 1;146(4):1079–1087. doi: 10.1084/jem.146.4.1079. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meruelo D., Nimelstein S. H., Jones P. P., Lieberman M., McDevitt H. O. Increased synthesis and expression of H-2 antigens on thymocytes as a result of radiation leukemia virus infection: a possible mechanism for H-2 linked control of virus-induced neoplasia. J Exp Med. 1978 Feb 1;147(2):470–487. doi: 10.1084/jem.147.2.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stockert E., Old L. J., Boyse E. A. The G-IX system. A cell surface allo-antigen associated with murine leukemia virus; implications regarding chromosomal integration of the viral genome. J Exp Med. 1971 Jun 1;133(6):1334–1355. doi: 10.1084/jem.133.6.1334. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Witte O. N., Weissman I. L. Polypeptides of Moloney sarcoma-leukemia virions: their resolution and incorporation into extracellular virions. Virology. 1974 Oct;61(2):575–587. doi: 10.1016/0042-6822(74)90291-8. [DOI] [PubMed] [Google Scholar]
- Zinkernagel R. M., Callahan G. N., Klein J., Dennert G. Cytotoxic T cells learn specificity for self H-2 during differentiation in the thymus. Nature. 1978 Jan 19;271(5642):251–253. doi: 10.1038/271251a0. [DOI] [PubMed] [Google Scholar]