BIOMAT Database Logo BIOMAT Database Logo

CD4+ T-cell development in a mouse expressing a transgenic TCR derived from a Treg. 2009

Richard J DiPaolo, and Ethan M Shevach
Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA. rdipaolo@slu.edu

CD4(+)Foxp3(+) Treg maintain peripheral tolerance and influence immune responses to foreign antigens. The thymus is an important source of Treg, but controversy exists as to whether T cells are selected into the Treg lineage based on signals received through TCR specific for self-peptides. To examine the specificity of TCR expressed by Treg and its effect on CD4(+) T-cell development, we generated Treg-TCR transgenic mice. Deletion of >90% of CD4(+) T cells in RAG-sufficient mice, and nearly 100% deletion in RAG(-/-) mice expressing this TCR indicate that the TCR is specific for an unknown, naturally expressed peptide in the thymus. Deletion occurs late in development, suggesting this peptide is presented by APC in the thymic medulla. These studies are the first to describe the effects of expressing a Treg-TCR on CD4(+) T-cell development. The implications of our data for models of Treg selection are discussed.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D011948 Receptors, Antigen, T-Cell Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (CD3 COMPLEX). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains. Antigen Receptors, T-Cell,T-Cell Receptors,Receptors, T-Cell Antigen,T-Cell Antigen Receptor,T-Cell Receptor,Antigen Receptor, T-Cell,Antigen Receptors, T Cell,Receptor, T-Cell,Receptor, T-Cell Antigen,Receptors, T Cell Antigen,Receptors, T-Cell,T Cell Antigen Receptor,T Cell Receptor,T Cell Receptors,T-Cell Antigen Receptors
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013950 Thymus Gland A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. Thymus,Gland, Thymus,Glands, Thymus,Thymus Glands
D015496 CD4-Positive T-Lymphocytes A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes. T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte
D017353 Gene Deletion A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. Deletion, Gene,Deletions, Gene,Gene Deletions
D050378 T-Lymphocytes, Regulatory CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells. Regulatory T Cell,Regulatory T-Cell,Regulatory T-Lymphocyte,Regulatory T-Lymphocytes,Suppressor T-Lymphocytes, Naturally-Occurring,T-Cells, Regulatory,Th3 Cells,Tr1 Cell,Treg Cell,Regulatory T-Cells,Suppressor T-Cells, Naturally-Occurring,Tr1 Cells,Treg Cells,Cell, Regulatory T,Cell, Th3,Cell, Tr1,Cell, Treg,Cells, Regulatory T,Cells, Th3,Cells, Tr1,Cells, Treg,Naturally-Occurring Suppressor T-Cell,Naturally-Occurring Suppressor T-Cells,Naturally-Occurring Suppressor T-Lymphocyte,Naturally-Occurring Suppressor T-Lymphocytes,Regulatory T Cells,Regulatory T Lymphocyte,Regulatory T Lymphocytes,Suppressor T Cells, Naturally Occurring,Suppressor T Lymphocytes, Naturally Occurring,Suppressor T-Cell, Naturally-Occurring,Suppressor T-Lymphocyte, Naturally-Occurring,T Cell, Regulatory,T Cells, Regulatory,T Lymphocytes, Regulatory,T-Cell, Naturally-Occurring Suppressor,T-Cells, Naturally-Occurring Suppressor,T-Lymphocyte, Regulatory,Th3 Cell
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018345 Mice, Knockout Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes. Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out

Related Publications

Richard J DiPaolo, and Ethan M Shevach
Disrupted development of thymocytes expressing a transgenic TCR upon CD4 overexpression.
December 1995, International immunology,
Richard J DiPaolo, and Ethan M Shevach
A clonal chondrocytic cell line derived from BMP-2/T antigen-expressing transgenic mouse.
May 1998, In vitro cellular & developmental biology. Animal,
Richard J DiPaolo, and Ethan M Shevach
Development of transgenic mice expressing a coronavirus-specific public CD4 T cell receptor.
October 2013, Journal of immunological methods,
Richard J DiPaolo, and Ethan M Shevach
Deficient CD4+ T cell proliferation in the class 1 MHC-restricted 2C TCR-transgenic mouse.
March 1996, Journal of immunology (Baltimore, Md. : 1950),
Richard J DiPaolo, and Ethan M Shevach
Comparison of a T cell clone and of T cells from a TCR transgenic mouse: TCR transgenic T cells specific for self-antigen are atypical.
February 2001, Journal of immunology (Baltimore, Md. : 1950),
Richard J DiPaolo, and Ethan M Shevach
T-cell receptor transgenic (TCR-Tg) mice from two diabetogenic CD4+ islet-antigen-specific T-cell clones.
March 2004, Journal of autoimmunity,
Richard J DiPaolo, and Ethan M Shevach
Allograft rejection in a new allospecific CD4+ TCR transgenic mouse.
April 2003, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons,
Richard J DiPaolo, and Ethan M Shevach
Retroviral vector expression in TCR transgenic CD4⁺ T cells.
January 2015, Methods in molecular biology (Clifton, N.J.),
Richard J DiPaolo, and Ethan M Shevach
Competition for specific intrathymic ligands limits positive selection in a TCR transgenic model of CD4+ T cell development.
June 2000, Journal of immunology (Baltimore, Md. : 1950),
Richard J DiPaolo, and Ethan M Shevach
The development and functions of CD4(+) T cells expressing a transgenic TCR specific for an MHC-I-restricted tumor antigenic epitope.
July 2011, Cellular & molecular immunology,
Copied contents to your clipboard!