Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1984 Sep 1;160(3):839–857. doi: 10.1084/jem.160.3.839

Self-recognition specificity expressed by T cells from nude mice. Absence of detectable Ia-restricted T cells in nude mice that do exhibit self-K/D-restricted T cell responses

PMCID: PMC2187392  PMID: 6206191

Abstract

The presence in athymic nude mice of precursor T cells with self- recognition specificity for either H-2 K/D or H-2 I region determinants was investigated. Chimeras were constructed of lethally irradiated parental mice receiving a mixture of F1 nude mouse (6-8 wk old) spleen and bone marrow cells. The donor inoculum was deliberately not subjected to any T cell depletion procedure, so that any potential major histocompatibility complex-committed precursor T cells were allowed to differentiate and expand in the normal parental recipients. 3 mo after reconstitution, the chimeras were immunized with several protein antigens in complete Freund's adjuvant in the footpads and their purified draining lymph node T cells tested 10 d later for ability to recognize antigen on antigen-presenting cells of either parental haplotype. Also, their spleen and lymph node cells were tested for ability to generate a cytotoxic T lymphocyte (CTL) response to trinitrophenyl (TNP)-modified stimulator cells of either parental haplotype. It was demonstrated that T cell proliferative responses of these F1(nude)----parent chimeras were restricted solely to recognizing parental host I region determinants as self and expressed the Ir gene phenotype of the host. In contrast, CTL responses could be generated (in the presence of interleukin 2) to TNP-modified stimulator cells of either parental haplotype. Thus these results indicate that nude mice which do have CTL with self-specificity for K/D region determinants lack proliferating T cells with self-specificity for I region determinants. These results provide evidence for the concepts that development of the I region-restricted T cell repertoire is strictly an intrathymically determined event and that young nude mice lack the unique thymic elements responsible for education of I region-restricted T cells.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. Ando I. Self-MHC-restricted cytotoxic T-cell response without thymic influence. Nature. 1981 Feb 5;289(5797):494–495. doi: 10.1038/289494a0. [DOI] [PubMed] [Google Scholar]
  2. Barclay A. N., Mayrhofer G. Bone marrow origin of Ia-positive cells in the medulla rat thymus. J Exp Med. 1981 Jun 1;153(6):1666–1671. doi: 10.1084/jem.153.6.1666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Billings P., Burakoff S. J., Dorf M. E., Benacerraf B. Genetic control of cytolytic T-lymphocyte responses. I. Ir gene control of the specificity of cytolytic T-lymphocyte responses to trinitrophenyl-modified syngeneic cells. J Exp Med. 1978 Aug 1;148(2):341–350. doi: 10.1084/jem.148.2.341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bradley S. M., Kruisbeek A. M., Singer A. Cytotoxic T lymphocyte responses in allogeneic radiation bone marrow chimeras. The chimeric host strictly dictates the self-repertoire of Ia-restricted T cells but not H-2K/D-restricted T cells. J Exp Med. 1982 Dec 1;156(6):1650–1664. doi: 10.1084/jem.156.6.1650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Corradin G., Etlinger H. M., Chiller J. M. Lymphocyte specificity to protein antigens. I. Characterization of the antigen-induced in vitro T cell-dependent proliferative response with lymph node cells from primed mice. J Immunol. 1977 Sep;119(3):1048–1053. [PubMed] [Google Scholar]
  8. Doherty P. C., Korngold R., Schwartz D. H., Bennink J. R. Development and loss of virus-specific thymic competence in bone marrow radiation chimeras and normal mice. Immunol Rev. 1981;58:37–72. doi: 10.1111/j.1600-065x.1981.tb00349.x. [DOI] [PubMed] [Google Scholar]
  9. Duprez V., Hamilton B., Burakoff S. J. Generation of cytolytic T lymphocytes in thymectomized, irradiated, and bone marrow-reconstituted mice. J Exp Med. 1982 Sep 1;156(3):844–859. doi: 10.1084/jem.156.3.844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Galli P., Dröge W. Development of cytotoxic T lymphocyte precursors in the absence of the thymus. Eur J Immunol. 1980 Feb;10(2):87–92. doi: 10.1002/eji.1830100204. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Glimcher L. H., Schwartz R. H., Longo D. L., Singer A. The specificity of the syngeneic mixed leukocyte response, a primary anti-I region T cell proliferative response, is determined intrathymically. J Immunol. 1982 Sep;129(3):987–991. [PubMed] [Google Scholar]
  14. Hedrick S. M., Watson J. Genetic control of the immune response to collagen. II. Antibody responses produced in fetal liver restored radiation chimeras and thymus reconstituted F1 hybrid nude mice. J Exp Med. 1979 Sep 19;150(3):646–652. doi: 10.1084/jem.150.3.646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hünig T., Bevan M. J. Specificity of cytotoxic T cells from athymic mice. J Exp Med. 1980 Sep 1;152(3):688–702. doi: 10.1084/jem.152.3.688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jenkinson E. J., Van Ewijk W., Owen J. J. Major histocompatibility complex antigen expression on the epithelium of the developing thymus in normal and nude mice. J Exp Med. 1981 Feb 1;153(2):280–292. doi: 10.1084/jem.153.2.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kappler J. W., Marrack P. The role of H-2 linked genes in helper T-cell function. IV. Importance of T-cell genotype and host environment in I-region and Ir gene expression. J Exp Med. 1978 Dec 1;148(6):1510–1522. doi: 10.1084/jem.148.6.1510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kappler J. W., Skidmore B., White J., Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981 May 1;153(5):1198–1214. doi: 10.1084/jem.153.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Klein J. R., Bevan M. J. Secretion of immune interferon and generation of cytotoxic T cell activity in nude mice are dependent on interleukin 2: age-associated endogenous production of interleukin 2 in nude mice. J Immunol. 1983 Apr;130(4):1780–1783. [PubMed] [Google Scholar]
  20. Kruisbeek A. M., Andrysiak P. M., Singer A. Self recognition of accessory cell Ia determinants is required for the in vitro generation of hapten-specific cytotoxic T lymphocyte responses. J Immunol. 1983 Oct;131(4):1650–1655. [PubMed] [Google Scholar]
  21. Kruisbeek A. M., Fultz M. J., Sharrow S. O., Singer A., Mond J. J. Early development of the T cell repertoire. In vivo treatment of neonatal mice with anti-Ia antibodies interferes with differentiation of I-restricted T cells but not K/D-restricted T cells. J Exp Med. 1983 Jun 1;157(6):1932–1946. doi: 10.1084/jem.157.6.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kruisbeek A. M., Sharrow S. O., Mathieson B. J., Singer A. The H-2 phenotype of the thymus dictates the self-specificity expressed by thymic but not splenic cytotoxic T lymphocyte precursors in thymus-engrafted nude mice. J Immunol. 1981 Nov;127(5):2168–2176. [PubMed] [Google Scholar]
  23. Kruisbeek A. M., Sharrow S. O., Singer A. Differences in the MHC-restricted self-recognition repertoire of intra-thymic and extra-thymic cytotoxic T lymphocyte precursors. J Immunol. 1983 Mar;130(3):1027–1032. [PubMed] [Google Scholar]
  24. Krönke M., Scheurich P., Pfizenmaier K., Röllinghoff M., Wagner H. T-T cell interactions during in vitro cytotoxic T lymphocyte responses. V. Precursor frequencies and specificity of alloreactive helper T cells. J Exp Med. 1982 Jul 1;156(1):41–54. doi: 10.1084/jem.156.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Longo D. L., Davis M. L. Early appearance of donor-type antigen-presenting cells in the thymuses of 1200 R radiation-induced bone marrow chimeras correlates with self-recognition of donor I region gene products. J Immunol. 1983 Jun;130(6):2525–2527. [PubMed] [Google Scholar]
  26. Longo D. L., Schwartz R. H. Gene complementation. Neither Ir-GLphi gene need be present in the proliferative T cell to generate an immune response to Poly(Glu55Lys36Phe9)n. J Exp Med. 1980 Jun 1;151(6):1452–1467. doi: 10.1084/jem.151.6.1452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Longo D. L., Schwartz R. H. Inhibition of antigen-induced proliferation of T cells from radiation-induced bone marrow chimeras by a monoclonal antibody directed against an Ia determinant on the antigen-presenting cell. Proc Natl Acad Sci U S A. 1981 Jan;78(1):514–518. doi: 10.1073/pnas.78.1.514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. MacDonald H. R., Lees R. K. Frequency and specificity of precursors of interleukin 2-producing cells in nude mice. J Immunol. 1984 Feb;132(2):605–610. [PubMed] [Google Scholar]
  29. Maryanski J. L., MacDonald H. R., Sordat B., Cerottini J. C. Cytolytic T lymphocyte precursor cells in congenitally athymic C57BL/6 nu/nu mice: quantitation, enrichment, and specificity. J Immunol. 1981 Mar;126(3):871–876. [PubMed] [Google Scholar]
  30. Ozato K., Mayer N., Sachs D. H. Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens. J Immunol. 1980 Feb;124(2):533–540. [PubMed] [Google Scholar]
  31. Ozato K., Sachs D. H. Monoclonal antibodies to mouse MHC antigens. III. Hybridoma antibodies reacting to antigens of the H-2b haplotype reveal genetic control of isotype expression. J Immunol. 1981 Jan;126(1):317–321. [PubMed] [Google Scholar]
  32. 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]
  33. Shearer G. M., Schmitt-Verhulst A. M., Pettinelli C. B., Miller M. W., Gilheany P. E. H-2-linked genetic control of murine T-cell-mediated lympholysis to autologous cells modified with low concentrations of trinitrobenzene sulfonate. J Exp Med. 1979 Jun 1;149(6):1407–1423. doi: 10.1084/jem.149.6.1407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Singer A., Hathcock K. S., Hodes R. J. Self recognition in allogeneic radiation bone marrow chimeras. A radiation-resistant host element dictates the self specificity and immune response gene phenotype of T-helper cells. J Exp Med. 1981 May 1;153(5):1286–1301. doi: 10.1084/jem.153.5.1286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Singer A., Hathcock K. S., Hodes R. J. Self recognition in allogeneic thymic chimeras. Self recognition by T helper cells from thymus-engrafted nude mice is restricted to the thymic H-2 haplotype. J Exp Med. 1982 Jan 1;155(1):339–344. doi: 10.1084/jem.155.1.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sprent J. Restricted helper function of F1 hybrid T cells positively selected to heterologous erythrocytes in irradiated parental strain mice. II. Evidence for restrictions affecting helper cell induction and T-B collaboration, both mapping to the K-end of the H-2 complex. J Exp Med. 1978 Apr 1;147(4):1159–1174. doi: 10.1084/jem.147.4.1159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wagner H., Hardt C., Stockinger H., Pfizenmaier K., Bartlett R., Röllinghoff M. Impact of thymus on the generation of immunocompetence and diversity of antigen-specific MHC-restricted cytotoxic T-lymphocyte precursors. Immunol Rev. 1981;58:95–129. doi: 10.1111/j.1600-065x.1981.tb00351.x. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. 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]

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

RESOURCES