Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1979 Jul;76(7):3477–3481. doi: 10.1073/pnas.76.7.3477

Biological effects of allogeneic effect factor on T lymphocytes: in vitro induction of cytotoxic T lymphocytes manifesting preferential lytic activity against H-2-identical tumor cells.

A Altman, T E Bechtold, J M Cardenas, D H Katz
PMCID: PMC383849  PMID: 315066

Abstract

The studies reported herein were designed to determine the effects of allogeneic effect factor (AEF), a soluble mediator generated in the course of allogeneic cell interactions, on the differentiation of cytotoxic T lymphocytes in vitro. Normal, unprimed spleen cells from various strains of mice cultured with AEF for 5 days, in the absence of any stimulator cells, developed into cytotoxic lymphocytes capable of lysing target cells in a short-term 51Cr release assay. T lymphocyte-depleted spleen cells did not become cytotoxic when cultured with AEF, and the cytotoxic cells themselves were found to be T lymphocytes. AEF-induced cytotoxic T lymphocytes preferentially lysed H-2-identical target cells. Thus, AEF, as opposed to similar "helper" factors derived from mixed lymphocyte cultures, appears to be unique in its ability to trigger normal, unprimed T lymphocytes to differentiate into cytotoxic T lymphocytes in the absence of specific antigenic stimulation.

Full text

PDF
3477

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altman A., Bechtold T. E., Katz D. H. Manipulation of cytotoxic T lymphocyte responses to syngeneic tumors. I. Hapten-reactive helper T lymphocytes augment tumor-specific CTL responses in vitro. J Immunol. 1979 Jun;122(6):2484–2490. [PubMed] [Google Scholar]
  2. Altman A., Cohen I. R. Cell-free media of mixed lymphocyte cultures augmenting sensitization in vitro of mouse T lymphocytes against allogeneic fibroblasts. Eur J Immunol. 1976 Jul;5(7):437–444. doi: 10.1002/eji.1830050702. [DOI] [PubMed] [Google Scholar]
  3. Armerding D., Katz D. H. Activation of T and B lymphocytes in vitro. II. Biological and biochemical properties of an allogeneic effect factor (AEF) active in triggering specific B lymphocytes. J Exp Med. 1974 Jul 1;140(1):19–37. doi: 10.1084/jem.140.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bach F. H., Bach M. L., Sondel P. M. Differential function of major histocompatibility complex antigens in T-lymphocyte activation. Nature. 1976 Jan 29;259(5541):273–281. doi: 10.1038/259273a0. [DOI] [PubMed] [Google Scholar]
  5. Bevan M. J., Langman R. E., Cohn M. H-2 antigen-specific cytotoxic T cells induced by concanavalin A: estimation of their relative frequency. Eur J Immunol. 1976 Mar;6(3):150–156. doi: 10.1002/eji.1830060303. [DOI] [PubMed] [Google Scholar]
  6. Bonavida B. Concanavalin A-mediated activation of antigen-primed lymphocytes into secondary cytotoxic lymphocytes. J Exp Med. 1977 Feb 1;145(2):293–301. doi: 10.1084/jem.145.2.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cantor H., Boyse E. A. Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J Exp Med. 1975 Jun 1;141(6):1390–1399. doi: 10.1084/jem.141.6.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clark W. R. An antigen-specific component of lectin-mediated cytotoxicity. Cell Immunol. 1975 Jun;17(2):505–516. doi: 10.1016/s0008-8749(75)80054-2. [DOI] [PubMed] [Google Scholar]
  9. Click R. E., Benck L., Alter B. J. Immune responses in vitro. I. Culture conditions for antibody synthesis. Cell Immunol. 1972 Feb;3(2):264–276. doi: 10.1016/0008-8749(72)90165-7. [DOI] [PubMed] [Google Scholar]
  10. Delovitch T. L., McDevitt H. O. In vitro analysis of allogeneic lymphocyte interaction. I. Characterization and cellular origin of an Ia-positive helper factor-allogeneic effect factor. J Exp Med. 1977 Oct 1;146(4):1019–1032. doi: 10.1084/jem.146.4.1019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Eshhar Z., Armerding D., Waks T., Katz D. H. Activation of T and B lymphocytes in vitro. V. Cellular locus, metabolism and genetics of induction, and production of the allogeneic effect factor. J Immunol. 1977 Oct;119(4):1457–1467. [PubMed] [Google Scholar]
  12. Finke J. H., Orosz C. G., Battisto J. R. Splenic T-killer cells can be generated by allogeneic thymic cells in conjunction with assisting factor. Nature. 1977 May 26;267(5609):353–354. doi: 10.1038/267353a0. [DOI] [PubMed] [Google Scholar]
  13. Friedman S. M., Kuhns J., Irigoyen O., Chess L. The induction of TNP-altered, self-reactive human cytotoxic T cells by soluble factors: the role of Ia antigens. J Immunol. 1979 Apr;122(4):1302–1309. [PubMed] [Google Scholar]
  14. Gillis S., Smith K. A. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977 Jul 14;268(5616):154–156. doi: 10.1038/268154a0. [DOI] [PubMed] [Google Scholar]
  15. Golstein P., Luciani M. F., Wagner H., Röllinghoff M. Mouse T cell-mediated cytolysis specifically triggered by cytophilic xenogeneic serum determinants: a caveat for the interpretation of experiments done under "syngeneic" conditions. J Immunol. 1978 Dec;121(6):2533–2538. [PubMed] [Google Scholar]
  16. Heininger D., Touton M., Chakravarty A. K., Clark W. R. Activation of cytotoxic function in T lymphocytes. J Immunol. 1976 Dec;117(6):2175–2180. [PubMed] [Google Scholar]
  17. Igarashi T., Okada M., Kishimoto T., Yamamura Y. In vitro induction of polyclonal killer T cells with 2-mercaptoethanol and the essential role of macrophages in this process. J Immunol. 1977 May;118(5):1697–1703. [PubMed] [Google Scholar]
  18. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  19. Katz D. H., Osborne D. P., Jr The allogeneic effect in inbred mice. II. Establishment of the cellular interactions required for enhancement of antibody production by the graft-versus-host reaction. J Exp Med. 1972 Sep 1;136(3):455–465. doi: 10.1084/jem.136.3.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Koopman W. J., Farrar J. J., Oppenheim J. J., Fuller-Bonar J., Dougherty S. Association of a low molecular weight helper factor(s) with thymocyte proliferative activity. J Immunol. 1977 Jul;119(1):55–60. [PubMed] [Google Scholar]
  21. L'age-Stehr J., Diamanstein T. Induction of autoreactive T lymphocytes and their suppressor cells by cyclophosphamide. Nature. 1978 Feb 16;271(5646):663–665. doi: 10.1038/271663a0. [DOI] [PubMed] [Google Scholar]
  22. Peck A. B., Andersson L. C., Wigzell H. Secondary in vitro responses of T lymphocytes to non-H-2 alloantigens self-H-2-restricted responses induced in heterologous serum are not dependent on primary-stimulating non-H-2 alloantigens. J Exp Med. 1977 Apr 1;145(4):802–818. doi: 10.1084/jem.145.4.802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Plate J. M. Soluble factors substitute for T-T-cell collaboration in generation of T-killer lymphocytes. Nature. 1976 Mar 25;260(5549):329–331. doi: 10.1038/260329a0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Shustik C., Cohen I. R., Schwartz R. S., Latham-Griffin E., Waksal S. D. T lymphocytes with promiscuous cytotoxicity. Nature. 1976 Oct 21;263(5579):699–701. doi: 10.1038/263699a0. [DOI] [PubMed] [Google Scholar]
  26. Simon P. L., Farrar J. J., Kind P. D. The xenogeneic effect. III. Induction of cell-mediated cytotoxicity by alloantigen-stimulated thymocytes in the presence of xenogeneic reconstitution factor. J Immunol. 1977 Apr;118(4):1129–1131. [PubMed] [Google Scholar]
  27. Sondel P. M., Jacobson M. W., Bach F. H. Selective activation of human suppressor cells by a nonproliferative stimulus. Eur J Immunol. 1977 Jan;7(1):38–40. doi: 10.1002/eji.1830070109. [DOI] [PubMed] [Google Scholar]
  28. Sopori M. L., Alter B. J., Bach F. H., Bach M. L. Cell-free factor substitute for "signal 2" in generating cytotoxic reactions. Eur J Immunol. 1977 Nov;7(11):823–825. doi: 10.1002/eji.1830071115. [DOI] [PubMed] [Google Scholar]
  29. Sopori M., Bernstein A., Bach F. H. In vitro sensitization of thymocytes. Role of H-21 I region determinants and cell-free mixed leukocyte culture supernates in generation of cytotoxic responses. J Exp Med. 1978 Oct 1;148(4):953–962. doi: 10.1084/jem.148.4.953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tartof D., Fitch F. W. Kinetics of CTL induction by concanavalin A. J Immunol. 1978 Apr;120(4):1086–1091. [PubMed] [Google Scholar]
  31. Wagner H., Röllinghoff M., Nossal G. J. T-cell-mediated immune responses induced in vitro: a probe for allograft and tumor immunity. Transplant Rev. 1973;17(0):3–36. doi: 10.1111/j.1600-065x.1973.tb00122.x. [DOI] [PubMed] [Google Scholar]
  32. Wagner H., Röllinghoff M. T-T-cell interactions during the vitro cytotoxic allograft responses. I. Soluble products from activated Lyl+ T cells trigger autonomously antigen-primed Ly23+ T cells to cell proliferation and cytolytic activity. J Exp Med. 1978 Dec 1;148(6):1523–1538. doi: 10.1084/jem.148.6.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Waterfield J. D., Waterfield E. M., Möller G. Lymphocyte-mediated cytotoxicity against tumor cells. I. Con A activated cytotoxic effector cells exhibit immunological specificity. Cell Immunol. 1975 Jun;17(2):392–404. doi: 10.1016/s0008-8749(75)80043-8. [DOI] [PubMed] [Google Scholar]
  34. Widmer M. B., Alter B. J., Bach F. H., Bach M. L. Lymphocyte reactivity to serologically undetected components of the major histocompatibility complex. Nat New Biol. 1973 Apr 25;242(121):239–241. doi: 10.1038/newbio242239a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES