Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1980 Sep 1;152(3):688–702. doi: 10.1084/jem.152.3.688

Specificity of cytotoxic T cells from athymic mice

PMCID: PMC2185925  PMID: 6447752

Abstract

In normal mice, self-H-2 antigens in the thymus have a profound influence on T cell specificity. We have therefore investigated the properties of cytotoxic T lymphocyte (CTL) precursors from athymic nude mice (5) with the notion that they may provide a model system for the study of T cells whose receptro specificity is closer to the germ-line- encoded repertoire. It was found that the precursors of nude CTL are, themselves, THy-1+ cells. The possibility that these nude t cells were derived from the phenotypically normal mother by placental transfer was ruled out. In the presence of T cell growth factor, nude CTL can be induced by polyclonal activation with concanavalin A or by stimulation with allogeneic or trinitrophenyl (TNP)-modified syngeneic stimulator cells, but not by stimulation with minor H antigens in the context of self-H-2. Alloreactive, nude CTL--like those from normal mice-- recognize H-2K- and H-2D-region-encoded antigens in killer-target cell interactions, but, unlike normal CTL, did not cross-react on third- party target cells. Whereas the anti-TNP response of nude mice is H-2 restricted, it does not seem to be influenced by self-H-2 antigens in the same manner as in normal mice. This is suggested by the finding that the immunodominance of H-2k over H-2d in the anti-TNP-self response of normal (H-2d X H-2b)F1 mice is absent in (H-2d X H-2k)F1 nude mice. These observations are discussed in relation to the role of the thymus in the generation of the normal mature T cell receptor repertoire.

Full Text

The Full Text of this article is available as a PDF (809.0 KB).

Selected References

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

  1. Asherson G. L., Ferluga J., Janossy G. Non-specific cytotoxicity by T cells activated with plant mitogens in vitro and the requirement for plant agents during the killing reaction. Clin Exp Immunol. 1973 Dec;15(4):573–589. [PMC free article] [PubMed] [Google Scholar]
  2. Bevan M. J., Cohn M. Cytotoxic effects of antigen- and mitogen-induced T cells on various targets. J Immunol. 1975 Feb;114(2 Pt 1):559–565. [PubMed] [Google Scholar]
  3. Bevan M. J., Fink P. J. The influence of thymus H-2 antigens on the specificity of maturing killer and helper cells. Immunol Rev. 1978;42:3–19. doi: 10.1111/j.1600-065x.1978.tb00256.x. [DOI] [PubMed] [Google Scholar]
  4. Bevan M. J. In a radiation chimaera, host H-2 antigens determine immune responsiveness of donor cytotoxic cells. Nature. 1977 Sep 29;269(5627):417–418. doi: 10.1038/269417a0. [DOI] [PubMed] [Google Scholar]
  5. Cantor H., Simpson E., Sato V. L., Fathman C. G., Herzenberg L. A. Characterization of subpopulations of T lymphocytes. I. Separation and functional studies of peripheral T-cells binding different amounts of fluorescent anti-Thy 1.2 (theta) antibody using a fluorescence-activated cell sorter (FACS). Cell Immunol. 1975 Jan;15(1):180–196. doi: 10.1016/0008-8749(75)90174-4. [DOI] [PubMed] [Google Scholar]
  6. Fink P. J., Bevan M. J. H-2 antigens of the thymus determine lymphocyte specificity. J Exp Med. 1978 Sep 1;148(3):766–775. doi: 10.1084/jem.148.3.766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Forman J., Vitetta E. S., Hart D. A., Klein J. Relationship between trinitrophenyl and H-2 antigens on trinitrophenyl-modified spleen cells. I. H-2 antigens on cells treated with trinitrobenzene sulfonic acid are derivatized. J Immunol. 1977 Mar;118(3):797–802. [PubMed] [Google Scholar]
  8. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Hünig T., Bevan M. J. Self H-2 antigens influence the specificity of alloreactive cells. J Exp Med. 1980 May 1;151(5):1288–1298. doi: 10.1084/jem.151.5.1288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ishikawa H., Saito K. Congenitally athymic nude (nu/nu) mice have Thy-1-bearing immunocompetent helper T cells in their peritoneal cavity. J Exp Med. 1980 Apr 1;151(4):965–968. doi: 10.1084/jem.151.4.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jerne N. K. The somatic generation of immune recognition. Eur J Immunol. 1971 Jan;1(1):1–9. doi: 10.1002/eji.1830010102. [DOI] [PubMed] [Google Scholar]
  14. Komuro K., Boyse E. A. Induction of T lymphocytes from precursor cells in vitro by a product of the thymus. J Exp Med. 1973 Aug 1;138(2):479–482. doi: 10.1084/jem.138.2.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Levy R. B., Shearer G. M. Regulation of T-cell-mediated lympholysis by the murine major histocompatibility complex. I. Preferential in vitro responses to trinitrophenyl-modified self K- and D-coded gene products in parental and F1 hybrid mouse strains. J Exp Med. 1979 Jun 1;149(6):1379–1392. doi: 10.1084/jem.149.6.1379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lindahl F., Peck A. B., Bach F. H. Specificity of cell-mediated lympholysis for public and private H-2 determinants. Scand J Immunol. 1975 Sep;4(5-6):541–553. doi: 10.1111/j.1365-3083.1975.tb02660.x. [DOI] [PubMed] [Google Scholar]
  17. Loor F., Amstutz H., Hägg L. B., Mayor K. S., Roelants G. E. T lineage lymphocytes in nude mice born from homozygous nu/nu parents. Eur J Immunol. 1976 Sep;6(9):663–665. doi: 10.1002/eji.1830060914. [DOI] [PubMed] [Google Scholar]
  18. Marshak-Rothstein A., Fink P., Gridley T., Raulet D. H., Bevan M. J., Gefter M. L. Properties and applications of monoclonal antibodies directed against determinants of the Thy-1 locus. J Immunol. 1979 Jun;122(6):2491–2497. [PubMed] [Google Scholar]
  19. Roelants G. E., Loor F., von Boehmer H., Sprent J., Hägg L. B., Mayor K. S., Rydén A. Five types of lymphocytes (Ig-theta-, Ig-theta+weak, Ig-theta+strong, Ig+theta- and Ig+theta+) characterized by double immunofluorescence and electrophoretic mobility. Organ distribution in normal and nude mice. Eur J Immunol. 1975 Feb;5(2):127–131. doi: 10.1002/eji.1830050211. [DOI] [PubMed] [Google Scholar]
  20. Sato V. L., Waksal S. D., Herzenberg L. A. Identification and separation of pre T-cells from nu/nu mice: differentiation by preculture with thymic reticuloepithelial cells. Cell Immunol. 1976 Jun 1;24(1):173–185. doi: 10.1016/0008-8749(76)90142-8. [DOI] [PubMed] [Google Scholar]
  21. Scheid M. P., Hoffmann M. K., Komuro K., Hämmerling U., Abbott J., Boyse E. A., Cohen G. H., Hooper J. A., Schulof R. S., Goldstein A. L. Differentiation of T cells induced by preparations from thymus and by nonthymic agents. J Exp Med. 1973 Oct 1;138(4):1027–1032. doi: 10.1084/jem.138.4.1027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Shearer G. M. Cell-mediated cytotoxicity to trinitrophenyl-modified syngeneic lymphocytes. Eur J Immunol. 1974 Aug;4(8):527–533. doi: 10.1002/eji.1830040802. [DOI] [PubMed] [Google Scholar]
  23. Simpson E., Mobraaten L., Chandler P., Hetherington C., Hurme M., Brunner C., Bailey D. Cross-reactive cytotoxic responses. H-2 restricted are more specific than anti-H-2 responses. J Exp Med. 1978 Dec 1;148(6):1478–1487. doi: 10.1084/jem.148.6.1478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Singh U., Owen J. J. Studies on the effect of various agents on the maturation of thymus stem cells. Eur J Immunol. 1975 Apr;5(4):286–288. doi: 10.1002/eji.1830050414. [DOI] [PubMed] [Google Scholar]
  25. Stutman O. Two main features of T-cell development: thymus traffic and postthymic maturation. Contemp Top Immunobiol. 1977;7:1–46. doi: 10.1007/978-1-4684-3054-7_1. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Zinkernagel R. M., Callahan G. N., Althage A., Cooper S., Klein P. A., Klein J. On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition? J Exp Med. 1978 Mar 1;147(3):882–896. doi: 10.1084/jem.147.3.882. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES