Abstract
Cytolytic T lymphocyte (CTL) clones specific for Moloney leukemia virus (MoLV)-derived tumor cells were generated by placing limiting numbers of C57BL/6 responder cells into mixed leukocyte-tumor cell microcultures. Under appropriate conditions (presence of stimulating tumor cells, accessory cells, and T cell growth factor), such cloned CTL could readily be expanded to provide large numbers of homogeneous, highly cytolytic CTL populations for further characterization. Using four target-cell types, three specificity patterns were observed: one reactive with the syngeneic MoLV-derived tumor only, one cross-reactive with an allogeneic MoLV-derived tumor, and one cross-reactive with normal allogeneic cells. Subclones derived from these three types of clones exhibited a high degree of stability in terms of lytic activity and specificity over a 4-mo period of observation. Three clones analyzed by flow cytofluorometry using monoclonal antibodies were all found to be of the Lyt-1+2+ phenotype. Furthermore, lysis of target cells by all of six clones tested was inhibited by anti-H-2Db (but not by anti-H-2Kb) monoclonal antibodies, demonstrating H-2Db-restriction at the clonal level.
Full Text
The Full Text of this article is available as a PDF (845.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brunner K. T., MacDonald H. R., Cerottini J. C. Antigenic specificity of the cytolytic T lymphocyte (CTL) response to murine sarcoma virus-induced tumors. II. Analysis of the clonal progeny of CTL precursors stimulated in vitro with syngeneic tumor cells. J Immunol. 1980 Apr;124(4):1627–1634. [PubMed] [Google Scholar]
- Cerottini J. C., Engers H. D., Macdonald H. R., Brunner T. Generation of cytotoxic T lymphocytes in vitro. I. Response of normal and immune mouse spleen cells in mixed leukocyte cultures. J Exp Med. 1974 Sep 1;140(3):703–717. doi: 10.1084/jem.140.3.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chesebro B., Wehrly K. Studies on the role of the host immune response in recovery from Friend virus leukemia. II. Cell-mediated immunity. J Exp Med. 1976 Jan 1;143(1):85–99. doi: 10.1084/jem.143.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillespie G. Y., Hansen C. B., Hoskins R. G., Russell S. W. Inflammatory cells in solid murine neoplasms. IV. Cytolytic T lymphocytes isolated from regressing or progressing Moloney sarcomas. J Immunol. 1977 Aug;119(2):564–570. [PubMed] [Google Scholar]
- Glasebrook A. L., Fitch F. W. Alloreactive cloned T cell lines. I. Interactions between cloned amplifier and cytolytic T cell lines. J Exp Med. 1980 Apr 1;151(4):876–895. doi: 10.1084/jem.151.4.876. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Glasebrook A. L., Fitch F. W. T-cell lines which cooperate in generation of specific cytolytic activity. Nature. 1979 Mar 8;278(5700):171–173. doi: 10.1038/278171a0. [DOI] [PubMed] [Google Scholar]
- Gomard E., Duprez V., Reme T., Colombani M. J., Levy J. P. Exclusive involvement of H-2Db or H-2Kd product in the interaction between T-killer lymphocytes and syngeneic H-2b or H-2d viral lymphomas. J Exp Med. 1977 Oct 1;146(4):909–922. doi: 10.1084/jem.146.4.909. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holden H. T., Haskill J. S., Kirchner H., Herberman R. B. Two functionally distinct anti-tumor effector cells isolated from primary murine sarcoma virus-induced tumors. J Immunol. 1976 Aug;117(2):440–446. [PubMed] [Google Scholar]
- Leclerc J. C., Cantor H. T cell-mediated immunity to oncornavirus-induced tumors. I. Ly phenotype of precursor and effector cytolytic T lymphocytes. J Immunol. 1980 Feb;124(2):846–850. [PubMed] [Google Scholar]
- Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
- Lemke H., Hämmerling G. J., Hämmerling U. Fine specificity analysis with monoclonal antibodies of antigens controlled by the major histocompatibility complex and by the Qa/TL region in mice. Immunol Rev. 1979;47:175–206. doi: 10.1111/j.1600-065x.1979.tb00293.x. [DOI] [PubMed] [Google Scholar]
- Levy J. P., Leclerc J. C. The murine sarcoma virus-induced tumor: exception or general model in tumor immunology? Adv Cancer Res. 1977;24:1–66. doi: 10.1016/s0065-230x(08)61012-x. [DOI] [PubMed] [Google Scholar]
- Lindahl K. F., Wilson D. B. Histocompatibility antigen-activated cytotoxic T lymphocytes. II. Estimates of the frequency and specificity of precursors. J Exp Med. 1977 Mar 1;145(3):508–522. doi: 10.1084/jem.145.3.508. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nabholz M., Conzelmann A., Acuto O., North M., Haas W., Pohlit H., von Boehmer H., Hengartner H., Mach J. P., Engers H. Established murine cytolytic T-cell lines as tools for a somatic cell genetic analysis of T-cell functions. Immunol Rev. 1980;51:125–156. doi: 10.1111/j.1600-065x.1980.tb00319.x. [DOI] [PubMed] [Google Scholar]
- Nakayama E., Shiku H., Stockert E., Oettgen H. F., Old L. J. Cytotoxic T cells: Lyt phenotype and blocking of killing activity by Lyt antisera. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1977–1981. doi: 10.1073/pnas.76.4.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Plata F., Cerottini J. C., Brunner K. T. Primary and secondary in vitro generation of cytolytic T lymphocytes in the murine sarcoma virus system. Eur J Immunol. 1975 Apr;5(4):227–233. doi: 10.1002/eji.1830050402. [DOI] [PubMed] [Google Scholar]
- Plata F., Jongeneel V., Cerottini J. C., Brunner K. T. Antigenic specificity of the cytolytic T lymphocyte (CTL) response to murine sarcoma virus-induced tumors. I. Preferential reactivity of in vitro generated secondary CTL with syngeneic tumor cells. Eur J Immunol. 1976 Nov;6(11):823–829. doi: 10.1002/eji.1830061114. [DOI] [PubMed] [Google Scholar]
- Plata F., Sordat B. Murine sarcoma virus (MSV)-induced tumors in mice. I. Distribution of MSV-immune cytolytic T lymphocytes in vivo. Int J Cancer. 1977 Feb 15;19(2):205–211. doi: 10.1002/ijc.2910190210. [DOI] [PubMed] [Google Scholar]
- Ryser J. E., Cerottini J. C., Brunner K. T. Generation of cytolytic T lymphocytes in vitro. IX. induction of secondary CTL responses in primary long-term MLC by supernatants from secondary MLC. J Immunol. 1978 Feb;120(2):370–377. [PubMed] [Google Scholar]
- Ryser J. E., MacDonald H. R. Limiting dilution analysis of alloantigen-reactive T lymphocytes. I. Comparison of precursor frequencies for proliferative and cytolytic responses. J Immunol. 1979 May;122(5):1691–1696. [PubMed] [Google Scholar]
- Schrader J. W., Edelman G. M. Participation of the H-2 antigens of tumor cells in their lysis by syngeneic T cells. J Exp Med. 1976 Mar 1;143(3):601–614. doi: 10.1084/jem.143.3.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Skinner M. A., Marbrook J. An estimation of the frequency of precursor cells which generate cytotoxic lymphocytes. J Exp Med. 1976 Jun 1;143(6):1562–1567. doi: 10.1084/jem.143.6.1562. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taniyama T., Holden H. T. In vitro induction of T-lymphocyte-mediated cytotoxicity by infectious murine type C oncornaviruses. J Exp Med. 1979 Dec 1;150(6):1367–1382. doi: 10.1084/jem.150.6.1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Teh H. S., Harley E., Phillips R. A., Miller R. G. Quantitative studies on the precursors of cytotoxic lymphocytes. I. Characterization of a clonal assay and determination of the size of clones derived from single precursors. J Immunol. 1977 Mar;118(3):1049–1056. [PubMed] [Google Scholar]