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PMID: 9524111 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The CD3gamma chain is essential for development of both the TCRalphabeta and TCRgammadelta lineages.

The EMBO journal ·Vol. 17 ·No. 7 ·1998-04-01 ·Pages 1871-82

Haks MC, Krimpenfort P, Borst J, Kruisbeek AM

Abstract

CD3gamma and CD3delta are the most closely related CD3 components, both of which participate in the TCRalphabeta-CD3 complex expressed on mature T cells. Interestingly, however, CD3delta does not appear to participate functionally in the pre-T-cell receptor (TCR) complex that is expressed on immature T cells: disruption of CD3delta gene expression has no effect on the developmental steps controlled by the pre-TCR. Here we report that in contrast with CD3delta, CD3gamma is an essential component of the pre-TCR. We generated mice selectively lacking expression of CD3gamma, in which expression of CD3delta, CD3epsilon, CD3zeta, pTalpha and TCRbeta remained undisturbed. Thus, all components for composing a pre-TCR are available, with the exception of CD3gamma. Nevertheless, T-cell development is severely inhibited in CD3gamma-deficient mice. The number of cells in the thymus is reduced to <1% of that in normal mice, and the large majority of thymocytes lack CD4 and CD8 and are arrested at the CD44-CD25+ double negative (DN) stage of development. Peripheral lymphoid organs are also practically devoid of T cells, with absolute numbers of peripheral T cells reduced to only 2-5% of those in normal mice. Both TCRalphabeta and TCRgammadelta lineages fail to develop effectively in CD3gamma-deficient mice, although absence of CD3gamma has no effect on gene rearrangements of the TCRbeta, delta and gamma loci. Furthermore, absence of CD3gamma results in a severe reduction in the level of TCR and CD3epsilon expression at the cell surface of thymocytes and peripheral T cells. The defect in the DN to double positive transition in mice lacking CD3gamma can be overcome by anti-CD3epsilon-mediated cross-linking. CD3gamma is thus essential for pre-TCR function.

MeSH Terms
Animals B-Lymphocytes/immunology CD3 Complex/blood,genetics,immunology CD4 Antigens/analysis CD8 Antigens/analysis Cell Lineage/immunology Gene Rearrangement, T-Lymphocyte Lymph Nodes/immunology Mice Mice, Knockout Organ Culture Techniques Phenotype RNA, Messenger/analysis Receptors, Antigen, T-Cell, alpha-beta/genetics,immunology Receptors, Antigen, T-Cell, gamma-delta/genetics,immunology Spleen/immunology T-Lymphocytes/immunology Thymus Gland/immunology
Chemicals
CD3 Complex CD4 Antigens CD8 Antigens RNA, Messenger Receptors, Antigen, T-Cell, alpha-beta Receptors, Antigen, T-Cell, gamma-delta
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Haks M C
Division of Immunology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Krimpenfort P
Borst J
Kruisbeek A M
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/17.7.1871
Published
1998-04-01
Pages
1871-82
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1170534
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/17.7.1871 PMC Full Text View journal details
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