Home LiteratureArticle Details
PMID: 8223445 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Developmental and functional impairment of T cells in mice lacking CD3 zeta chains.

The EMBO journal ·Vol. 12 ·No. 11 ·1993-11-00 ·Pages 4357-66

Ohno H, Aoe T, Taki S, Kitamura D, Ishida Y, Rajewsky K, Saito T

Abstract

CD3 zeta is a component of the T cell antigen receptor (TCR) complex and is important for signal transduction. We have established mice selectively lacking CD3 zeta but able to express CD3 eta, a polypeptide produced from the same locus through alternative splicing, using the method of gene targeting in embryonic stem cells. In homozygous mutant mice, the numbers of thymocytes and peripheral T cells were greatly reduced and the expression levels of TCR on these cells were 5-fold lower than those on wild-type cells. By contrast, TCR gamma delta+ intestinal intraepithelial lymphocytes were not obviously affected by the mutation. T cells from homozygous mutants exhibited an impaired proliferative response. These results imply that CD3 zeta has a critical role in the development and signal transduction of T cells in vivo.

MeSH Terms
Animals Base Sequence Blood Cells/cytology,immunology CD3 Complex/genetics Homozygote Intestines/cytology,embryology,immunology Lymphocyte Activation Mice Mice, Inbred C57BL Molecular Sequence Data Receptors, Antigen, T-Cell/genetics Signal Transduction Stem Cells T-Lymphocytes/immunology Thymus Gland/cytology,embryology,immunology
Chemicals
CD3 Complex Receptors, Antigen, T-Cell
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Ohno H
Division of Molecular Genetics, Chiba University, School of Medicine, Japan.
Aoe T
Taki S
Kitamura D
Ishida Y
Rajewsky K
Saito T
References (47)
47 references, click to expand
  1. A rapid method for the isolation of functional thymus-derived murine lymphocytes.
    Eur J Immunol. 1973 Oct;3(10):645-9 PMID: 4587740
  2. CD3 eta and CD3 zeta are alternatively spliced products of a common genetic locus and are transcriptionally and/or post-transcriptionally regulated during T-cell development.
    Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5202-6 PMID: 1828894
  3. Characterization of an anti-peptide antibody that recognizes the murine analogue of the human T cell antigen receptor-T3 delta-chain.
    J Immunol. 1986 Nov 15;137(10):3254-8 PMID: 3095425
  4. Building a multichain receptor: synthesis, degradation, and assembly of the T-cell antigen receptor.
    Proc Natl Acad Sci U S A. 1987 May;84(9):2688-92 PMID: 3495001
  5. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  6. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells.
    Cell. 1987 Nov 6;51(3):503-12 PMID: 2822260
  7. Failure to synthesize the T cell CD3-zeta chain: structure and function of a partial T cell receptor complex.
    Cell. 1988 Jan 15;52(1):85-95 PMID: 3278811
  8. T cell CD3-zeta eta heterodimer expression and coupling to phosphoinositide hydrolysis.
    Science. 1988 Oct 28;242(4878):571-4 PMID: 2845582
  9. Engagement of the CD4 molecule influences cell surface expression of the T-cell receptor on thymocytes.
    Nature. 1988 Nov 3;336(6194):76-9 PMID: 3263575
  10. T-cell receptor isoforms and signal transduction.
    Curr Opin Immunol. 1991 Feb;3(1):32-9 PMID: 1828948
  11. Mice lacking MHC class II molecules.
    Cell. 1991 Sep 6;66(5):1051-66 PMID: 1909605
  12. Novel function for intestinal intraepithelial lymphocytes. Murine CD3+, gamma/delta TCR+ T cells produce IFN-gamma and IL-5.
    J Immunol. 1991 Dec 1;147(11):3736-44 PMID: 1682383
  13. Ligand-stimulated signaling events in immature CD4+CD8+ thymocytes expressing competent T-cell receptor complexes.
    Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9949-53 PMID: 1719558
  14. Generation and analysis of interleukin-4 deficient mice.
    Science. 1991 Nov 1;254(5032):707-10 PMID: 1948049
  15. Structural similarity between Fc receptors and T cell receptors. Expression of the gamma-subunit of Fc epsilon RI in human T cells, natural killer cells and thymocytes.
    J Immunol. 1991 Dec 15;147(12):4263-70 PMID: 1836482
  16. T cell receptor complexes containing Fc epsilon RI gamma homodimers in lieu of CD3 zeta and CD3 eta components: a novel isoform expressed on large granular lymphocytes.
    J Exp Med. 1992 Jan 1;175(1):203-9 PMID: 1530959
  17. The T cell receptor/CD3 complex is composed of at least two autonomous transduction modules.
    Cell. 1992 Jan 10;68(1):83-95 PMID: 1531041
  18. Cell autonomous expression of IgD is not essential for the maturation of conventional B cells.
    Int Immunol. 1991 Dec;3(12):1367-71 PMID: 1838007
  19. Extrathymic differentiation of intraepithelial lymphocytes: generation of a separate and unequal T-cell repertoire?
    Immunol Today. 1991 Dec;12(12):436-8 PMID: 1786079
  20. A population of early fetal thymocytes expressing Fc gamma RII/III contains precursors of T lymphocytes and natural killer cells.
    Cell. 1992 Apr 3;69(1):139-50 PMID: 1532536
  21. Production of homozygous mutant ES cells with a single targeting construct.
    Mol Cell Biol. 1992 May;12(5):2391-5 PMID: 1569957
  22. A critical role of lambda 5 protein in B cell development.
    Cell. 1992 May 29;69(5):823-31 PMID: 1591779
  23. The gamma-zeta dimers of Fc receptors as connectors to signal transduction.
    Curr Opin Immunol. 1992 Feb;4(1):43-8 PMID: 1534484
  24. Instability of assembled T-cell receptor complex that is associated with rapid degradation of zeta chains in immature CD4+CD8+ thymocytes.
    Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9494-8 PMID: 1357664
  25. Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages.
    Nature. 1992 Nov 19;360(6401):225-31 PMID: 1359428
  26. Differential regulation of T-cell receptor processing and surface expression affected by CD3 theta, an alternatively spliced product of the CD3 zeta/eta gene locus.
    J Biol Chem. 1992 Dec 25;267(36):26023-30 PMID: 1464613
  27. The extrathymic T-cell development pathway.
    Immunol Today. 1992 Nov;13(11):449-54 PMID: 1476600
  28. Subcellular localization of T-cell receptor complexes containing tyrosine-phosphorylated zeta proteins in immature CD4+CD8+ thymocytes.
    Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2438-42 PMID: 7681596
  29. Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes.
    Nature. 1988 Nov 24;336(6197):348-52 PMID: 3194019
  30. Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells.
    Nature. 1988 Dec 15;336(6200):684-7 PMID: 3143916
  31. Antigen receptor tail clue.
    Nature. 1989 Mar 30;338(6214):383-4 PMID: 2927501
  32. Intrathymic signalling in immature CD4+CD8+ thymocytes results in tyrosine phosphorylation of the T-cell receptor zeta chain.
    Nature. 1989 Oct 19;341(6243):651-4 PMID: 2477711
  33. Activation-driven programmed cell death and T cell receptor zeta eta expression.
    Science. 1989 Dec 1;246(4934):1162-5 PMID: 2531464
  34. The implications of subunit interactions for the structure of the T cell receptor-CD3 complex.
    Eur J Immunol. 1990 Feb;20(2):299-305 PMID: 2138083
  35. Novel post-translational regulation of TCR expression in CD4+CD8+ thymocytes influenced by CD4.
    Nature. 1990 Mar 15;344(6263):247-51 PMID: 1690353
  36. The role of the T cell receptor in positive and negative selection of developing T cells.
    Science. 1990 Jun 15;248(4961):1335-41 PMID: 1972592
  37. Family of disulphide-linked dimers containing the zeta and eta chains of the T-cell receptor and the gamma chain of Fc receptors.
    Nature. 1990 Sep 13;347(6289):189-91 PMID: 2203969
  38. Structure of the T-cell antigen receptor: evidence for two CD3 epsilon subunits in the T-cell receptor-CD3 complex.
    Proc Natl Acad Sci U S A. 1990 Sep;87(18):7220-4 PMID: 2144901
  39. Inhibition of T cell receptor expression and function in immature CD4+CD8+ cells by CD4.
    Science. 1990 Sep 28;249(4976):1558-61 PMID: 2120773
  40. Structure of the T cell antigen receptor (TCR): two CD3 epsilon subunits in a functional TCR/CD3 complex.
    J Exp Med. 1991 Jan 1;173(1):7-17 PMID: 1824636
  41. Cellular immunity to HIV activated by CD4 fused to T cell or Fc receptor polypeptides.
    Cell. 1991 Mar 8;64(5):1037-46 PMID: 1900456
  42. The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal transduction pathways.
    Cell. 1991 Mar 8;64(5):891-901 PMID: 1705867
  43. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene.
    Nature. 1991 Apr 4;350(6317):423-6 PMID: 1901381
  44. CD3 zeta and eta chains are produced by alternative splicing from a common gene.
    Int Immunol. 1990;2(11):1117-9 PMID: 2150596
  45. Major histocompatibility complex class II hyperexpression on B cells in interleukin 4-transgenic mice does not lead to B cell proliferation and hypergammaglobulinemia.
    Eur J Immunol. 1991 Apr;21(4):921-5 PMID: 2019289
  46. Differential signal transduction via T-cell receptor CD3 zeta 2, CD3 zeta-eta, and CD3 eta 2 isoforms.
    Proc Natl Acad Sci U S A. 1991 May 1;88(9):3842-6 PMID: 1708889
  47. The role of the T3/antigen receptor complex in T-cell activation.
    Annu Rev Immunol. 1986;4:593-619 PMID: 2939858
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1993-11-00
Pages
4357-66
Language
English
Region
England
NLM ID
8208664
PMCID
PMC413732
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]