Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1982 Aug 1;156(2):610–621. doi: 10.1084/jem.156.2.610

Primary in vitro cytotoxic T cell response to non-major histocompatibility complex alloantigens in normal mice

PMCID: PMC2186758  PMID: 6980257

Abstract

We have shown for the first time that it is possible to consistently generate a primary in vitro cytotoxic T cell (Tc) response to non-major histocompatibility complex alloantigens using responder cells from a normal mouse strain. This was achieved by carrying out, in the generating phase, a limiting dilution procedure in which it appears that suppressor cells that inhibit Tc activation or expansion are too dilute to manifest their effect. Moreover, the response was observed in mouse serum-(MS) as well as fetal calf serum- (FCS) supplemented media, an important finding in the light of the anomalous nonspecific effects induced by FCS. The cytotoxic response produced in MS-supplemented media was shown to be highly specific in both the generating and effector phases, whereas the responses in FCS had a strong nonspecific component.

Full Text

The Full Text of this article is available as a PDF (780.7 KB).

Selected References

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

  1. Bevan M. J. Interaction antigens detected by cytotoxic T cells with the major histocompatibility complex as modifier. Nature. 1975 Jul 31;256(5516):419–421. doi: 10.1038/256419a0. [DOI] [PubMed] [Google Scholar]
  2. Botzenhardt U., Klein J., Ziff M. Primary in vitro cell-mediated lympholysis reaction of NZB mice against unmodified targets syngeneic at the major histocompatibility complex. J Exp Med. 1978 May 1;147(5):1435–1448. doi: 10.1084/jem.147.5.1435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Festenstein H. Immunogenetic and biological aspects of in vitro lymphocyte allotransformation (MLR) in the mouse. Transplant Rev. 1973;15:62–88. doi: 10.1111/j.1600-065x.1973.tb00111.x. [DOI] [PubMed] [Google Scholar]
  4. Forni G., Green I. Heterologous sera: a target for in vitro cell-mediated cytotoxicity. J Immunol. 1976 Jun;116(6):1561–1565. [PubMed] [Google Scholar]
  5. Gillis S., Union N. A., Baker P. E., Smith K. A. The in vitro generation and sustained culture of nude mouse cytolytic T-lymphocytes. J Exp Med. 1979 Jun 1;149(6):1460–1476. doi: 10.1084/jem.149.6.1460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Golstein P., Rubin B., Denizot F., Luciani M. F. Xenoserum-induced cytolytic "T" cells: polyclonal specificity with an apparent "anti-self" component, and cooperative induction. Immunobiology. 1979 Aug;156(1-2):121–137. [PubMed] [Google Scholar]
  8. Gordon R. D., Simpson E., Samelson L. E. In vitro cell-mediated immune responses to the male specific(H-Y) antigen in mice. J Exp Med. 1975 Nov 1;142(5):1108–1120. doi: 10.1084/jem.142.5.1108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hardt C., Röllinghoff M., Pfizenmaier K., Mosmann H., Wagner H. Lyt-23+ cyclophosphamide-sensitive T cells regulate the activity of an interleukin 2 inhibitor in vivo. J Exp Med. 1981 Aug 1;154(2):262–274. doi: 10.1084/jem.154.2.262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hayes C. E., Macphail S., Bach F. H. Generation of primary cytotoxic lymphocytes against non-major histocompatibility complex antigens by anti-Ia serum plus complement-treated lymphocytes. J Exp Med. 1980 May 1;151(5):1305–1310. doi: 10.1084/jem.151.5.1305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lindahl K. F., Hausmann B. Qed-1--a target for unrestricted killing by T cells. Eur J Immunol. 1980 Apr;10(4):289–298. doi: 10.1002/eji.1830100413. [DOI] [PubMed] [Google Scholar]
  12. MacDonald H. R., Cerottini J. C., Ryser J. E., Maryanski J. L., Taswell C., Widmer M. B., Brunner K. T. Quantitation and cloning of cytolytic T lymphocytes and their precursors. Immunol Rev. 1980;51:93–123. doi: 10.1111/j.1600-065x.1980.tb00318.x. [DOI] [PubMed] [Google Scholar]
  13. Macphail S. Non-H-2 T-lymphocyte-mediated cytotoxicity after primary in vivo sensitization. Scand J Immunol. 1980;12(4):303–308. doi: 10.1111/j.1365-3083.1980.tb00071.x. [DOI] [PubMed] [Google Scholar]
  14. Miller R. A., Stutman O. Enumeration of IL 2-secreting helper T cells by limiting dilution analysis, and demonstration of unexpectedly high levels of IL 2 production per responding cell. J Immunol. 1982 May;128(5):2258–2264. [PubMed] [Google Scholar]
  15. Miller R. G., Dunkley M. Quantitative analysis of the 51Cr release cytotoxicity assay for cytotoxic lymphocytes. Cell Immunol. 1974 Nov;14(2):284–302. doi: 10.1016/0008-8749(74)90212-3. [DOI] [PubMed] [Google Scholar]
  16. Miller R. G., Teh H. S., Harley E., Phillips R. A. Quantitative studies of the activation of cytotoxic lymphocyte precursor cells. Immunol Rev. 1977;35:38–58. doi: 10.1111/j.1600-065x.1977.tb00234.x. [DOI] [PubMed] [Google Scholar]
  17. Mills G. B., Paetkau V. Generation of cytotoxic lymphocytes to syngeneic tumor by using co-stimulator (Interleukin 2). J Immunol. 1980 Nov;125(5):1897–1903. [PubMed] [Google Scholar]
  18. 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]
  19. Peck A. B., Bach F. H. A miniaturized mouse mixed leukocyte culture in serum-free and mouse serum supplemented media. J Immunol Methods. 1973 Oct;3(2):147–163. doi: 10.1016/0022-1759(73)90030-6. [DOI] [PubMed] [Google Scholar]
  20. Rich R. R., Sedberry D. A., Kastner D. L., Chu L. Primary in vitro cytotoxic response of NZB spleen cells to Qa-1b-associated antigenic determinants. J Exp Med. 1979 Dec 1;150(6):1555–1560. doi: 10.1084/jem.150.6.1555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Spiess P. J., Rosenberg S. A. A simplified method for the production of murine T-cell growth factor free of lectin. J Immunol Methods. 1981;42(2):213–222. doi: 10.1016/0022-1759(81)90151-4. [DOI] [PubMed] [Google Scholar]
  22. Stockinger B., Botzenhardt U. On the T cell hyperreactivity of NZB mice against H-2-identical cells. Evidence for primary response characteristics and an increased helper potential. J Exp Med. 1980 Aug 1;152(2):296–305. doi: 10.1084/jem.152.2.296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Teh H. S., Teh S. J. The use of a clonal assay for cytotoxic T lymphocytes to determine the Ly phenotypes of the cytotoxic precursor and effector cells to alloantigens and trinitrophenyl-modified self antigens. J Immunol. 1980 Nov;125(5):1977–1986. [PubMed] [Google Scholar]
  24. Theofilopoulos A. N., Shawler D. L., Katz D. H., Dixon F. J. Patterns of immune reactivity in autoimmune murine strains. I. Cell-mediated immune responses induced by H-2 indentical and H-2 incompatible stimulator cells. J Immunol. 1979 Jun;122(6):2319–2327. [PubMed] [Google Scholar]
  25. 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]
  26. Weyand C., Goronzy J., Hämmerling G. J. Recognition of polymorphic H-2 domains by T lymphocytes. I. Functional role of different H-2 domains for the generation of alloreactive cytotoxic T lymphocytes and determination of precursor frequencies. J Exp Med. 1981 Dec 1;154(6):1717–1731. doi: 10.1084/jem.154.6.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES