Skip to main content
PMC home page
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
. 1991 Jan 15;88(2):608–612. doi: 10.1073/pnas.88.2.608

Expression of CD4 in transgenic mice alters the specificity of CD8 cells for allogeneic major histocompatibility complex.

E Robey 1, F Ramsdell 1, J Elliott 1, D Raulet 1, D Kioussis 1, R Axel 1, B J Fowlkes 1
PMCID: PMC50861  PMID: 1824875

Abstract

We have generated a transgenic mouse line in which a CD4 transgene is expressed on a significant fraction of the mature CD8+ lymphocytes but is not expressed in the thymus. This provides an opportunity to examine the functional consequences of CD4 expression in a population of class I-selected CD8+ lymphocytes. CD8+ lymphocytes expressing the CD4 transgene proliferate in response to allogeneic class I and class II major histocompatibility complex, whereas CD8+ cells from control animals proliferate only to allogeneic class I gene products. These observations suggest that the ability of a T-cell population to react with class II allogeneic major histocompatibility complex is determined by the presence of CD4.

Full text

PDF

Images in this article

609Image
on p.609
609Image
on p.609
610Image
on p.610
610Image
on p.610
611Image
on p.611

Selected References

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

  1. Bottomly K., Luqman M., Greenbaum L., Carding S., West J., Pasqualini T., Murphy D. B. A monoclonal antibody to murine CD45R distinguishes CD4 T cell populations that produce different cytokines. Eur J Immunol. 1989 Apr;19(4):617–623. doi: 10.1002/eji.1830190407. [DOI] [PubMed] [Google Scholar]
  2. Brown J. H., Jardetzky T., Saper M. A., Samraoui B., Bjorkman P. J., Wiley D. C. A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature. 1988 Apr 28;332(6167):845–850. doi: 10.1038/332845a0. [DOI] [PubMed] [Google Scholar]
  3. Charnay P., Mellon P., Maniatis T. Linker scanning mutagenesis of the 5'-flanking region of the mouse beta-major-globin gene: sequence requirements for transcription in erythroid and nonerythroid cells. Mol Cell Biol. 1985 Jun;5(6):1498–1511. doi: 10.1128/mcb.5.6.1498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chothia C., Boswell D. R., Lesk A. M. The outline structure of the T-cell alpha beta receptor. EMBO J. 1988 Dec 1;7(12):3745–3755. doi: 10.1002/j.1460-2075.1988.tb03258.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dembić Z., Haas W., Weiss S., McCubrey J., Kiefer H., von Boehmer H., Steinmetz M. Transfer of specificity by murine alpha and beta T-cell receptor genes. Nature. 1986 Mar 20;320(6059):232–238. doi: 10.1038/320232a0. [DOI] [PubMed] [Google Scholar]
  6. Dembić Z., Haas W., Zamoyska R., Parnes J., Steinmetz M., von Boehmer H. Transfection of the CD8 gene enhances T-cell recognition. Nature. 1987 Apr 2;326(6112):510–511. doi: 10.1038/326510a0. [DOI] [PubMed] [Google Scholar]
  7. Doyle C., Strominger J. L. Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature. 1987 Nov 19;330(6145):256–259. doi: 10.1038/330256a0. [DOI] [PubMed] [Google Scholar]
  8. Emmrich F., Strittmatter U., Eichmann K. Synergism in the activation of human CD8 T cells by cross-linking the T-cell receptor complex with the CD8 differentiation antigen. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8298–8302. doi: 10.1073/pnas.83.21.8298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gabert J., Langlet C., Zamoyska R., Parnes J. R., Schmitt-Verhulst A. M., Malissen B. Reconstitution of MHC class I specificity by transfer of the T cell receptor and Lyt-2 genes. Cell. 1987 Aug 14;50(4):545–554. doi: 10.1016/0092-8674(87)90027-4. [DOI] [PubMed] [Google Scholar]
  10. Gao E. K., Kanagawa O., Sprent J. Capacity of unprimed CD4+ and CD8+ T cells expressing V beta 11 receptors to respond to I-E alloantigens in vivo. J Exp Med. 1989 Dec 1;170(6):1947–1957. doi: 10.1084/jem.170.6.1947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gay D., Maddon P., Sekaly R., Talle M. A., Godfrey M., Long E., Goldstein G., Chess L., Axel R., Kappler J. Functional interaction between human T-cell protein CD4 and the major histocompatibility complex HLA-DR antigen. Nature. 1987 Aug 13;328(6131):626–629. doi: 10.1038/328626a0. [DOI] [PubMed] [Google Scholar]
  12. Golding H., Mizuochi T., McCarthy S. A., Cleveland C. A., Singer A. Relationship among function, phenotype, and specificity in primary allospecific T cell populations: identification of phenotypically identical but functionally distinct primary T cell subsets that differ in their recognition of MHC class I and class II allodeterminants. J Immunol. 1987 Jan 1;138(1):10–17. [PubMed] [Google Scholar]
  13. Greaves D. R., Wilson F. D., Lang G., Kioussis D. Human CD2 3'-flanking sequences confer high-level, T cell-specific, position-independent gene expression in transgenic mice. Cell. 1989 Mar 24;56(6):979–986. doi: 10.1016/0092-8674(89)90631-4. [DOI] [PubMed] [Google Scholar]
  14. Hayakawa K., Hardy R. R. Murine CD4+ T cell subsets defined. J Exp Med. 1988 Nov 1;168(5):1825–1838. doi: 10.1084/jem.168.5.1825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Heeg K., Steeg C., Schmitt J., Wagner H. Frequency analysis of class I MHC-reactive Lyt-2+ and class II MHC-reactive L3T4+ IL 2-secreting T lymphocytes. J Immunol. 1987 Jun 15;138(12):4121–4127. [PubMed] [Google Scholar]
  16. Kanagawa O., Maki R. Inhibition of MHC class II-restricted T cell response by Lyt-2 alloantigen. J Exp Med. 1989 Sep 1;170(3):901–912. doi: 10.1084/jem.170.3.901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Liao N. S., Maltzman J., Raulet D. H. Positive selection determines T cell receptor V beta 14 gene usage by CD8+ T cells. J Exp Med. 1989 Jul 1;170(1):135–143. doi: 10.1084/jem.170.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Macdonald P. M., Ingham P., Struhl G. Isolation, structure, and expression of even-skipped: a second pair-rule gene of Drosophila containing a homeo box. Cell. 1986 Dec 5;47(5):721–734. doi: 10.1016/0092-8674(86)90515-5. [DOI] [PubMed] [Google Scholar]
  19. Macphail S., Stutman O. L3T4+ cytotoxic T lymphocytes specific for class I H-2 antigens are activated in primary mixed lymphocyte reactions. J Immunol. 1987 Dec 15;139(12):4007–4015. [PubMed] [Google Scholar]
  20. Mage M. G. Separation of lymphocytes on antibody-coated plates. Methods Enzymol. 1984;108:118–124. [PubMed] [Google Scholar]
  21. Norment A. M., Salter R. D., Parham P., Engelhard V. H., Littman D. R. Cell-cell adhesion mediated by CD8 and MHC class I molecules. Nature. 1988 Nov 3;336(6194):79–81. doi: 10.1038/336079a0. [DOI] [PubMed] [Google Scholar]
  22. Saito T., Weiss A., Miller J., Norcross M. A., Germain R. N. Specific antigen-Ia activation of transfected human T cells expressing murine Ti alpha beta-human T3 receptor complexes. Nature. 1987 Jan 8;325(7000):125–130. doi: 10.1038/325125a0. [DOI] [PubMed] [Google Scholar]
  23. Salter R. D., Benjamin R. J., Wesley P. K., Buxton S. E., Garrett T. P., Clayberger C., Krensky A. M., Norment A. M., Littman D. R., Parham P. A binding site for the T-cell co-receptor CD8 on the alpha 3 domain of HLA-A2. Nature. 1990 May 3;345(6270):41–46. doi: 10.1038/345041a0. [DOI] [PubMed] [Google Scholar]
  24. Schilham M. W., Lang R., Benner R., Zinkernagel R. M., Hengartner H. Characterization of an Lyt-2+ alloreactive cytotoxic T cell clone specific for H-2Db that cross-reacts with I-Ek. J Immunol. 1986 Nov 1;137(9):2748–2754. [PubMed] [Google Scholar]
  25. Sleckman B. P., Peterson A., Jones W. K., Foran J. A., Greenstein J. L., Seed B., Burakoff S. J. Expression and function of CD4 in a murine T-cell hybridoma. Nature. 1987 Jul 23;328(6128):351–353. doi: 10.1038/328351a0. [DOI] [PubMed] [Google Scholar]
  26. Sprent J., Schaefer M. Properties of purified T cell subsets. I. In vitro responses to class I vs. class II H-2 alloantigens. J Exp Med. 1985 Dec 1;162(6):2068–2088. doi: 10.1084/jem.162.6.2068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sprent J., Webb S. R. Function and specificity of T cell subsets in the mouse. Adv Immunol. 1987;41:39–133. doi: 10.1016/s0065-2776(08)60030-9. [DOI] [PubMed] [Google Scholar]
  28. Sredni B., Schwartz R. H. Alloreactivity of an antigen-specific T-cell clone. Nature. 1980 Oct 30;287(5785):855–857. doi: 10.1038/287855a0. [DOI] [PubMed] [Google Scholar]
  29. von Boehmer H., Hengartner H., Nabholz M., Lernhardt W., Schreier M. H., Haas W. Fine specificity of a continuously growing killer cell clone specific for H-Y antigen. Eur J Immunol. 1979 Aug;9(8):592–597. doi: 10.1002/eji.1830090804. [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