T cell lineages in the thymus of lpr/lpr mice. Evidence for parallel pathways of normal and abnormal T cell development. 1987

R C Budd, and M Schreyer, and G C Miescher, and H R MacDonald
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.

Autoimmune mice homozygous for the lpr/lpr (lpr) gene develop a profound lymphadenopathy resulting from the accumulation of immature Thy-1+ Lyt-2- L3T4- cells in peripheral lymphoid tissues. The source of these cells is not known although the presence of a thymus is necessary to manifest both the lymph node enlargement and the autoimmunity. For this reason and the fact that the abnormal lpr cell phenotypically resembles immature thymocytes, we studied the thymus in lpr mice. Adult lpr thymuses were found to contain an immature population phenotypically identical to the peripherally accumulating cells, including the expression of B220 and Pgp-1 antigens as well as the presence of surface T cell receptor molecules as defined by the antibody KJ16-133. Evidence is presented that some of these lpr precursor T cells are capable of intrathymic differentiation, whereas the vast majority are exported unchanged to the lymph nodes where a portion differentiate further into mature T cells. This lpr-specific lineage could be distinguished from a normal component of the lpr thymus by surface phenotype and immunohistology. The results suggest that the massive accumulation of cells in lpr lymph nodes is not so much the result of abnormal proliferation of T cells as abnormal intrathymic differentiation. In addition, a minor subpopulation of normal Lyt-2- L3T4- thymocytes was identified that resembles the phenotype of the lpr cell and similarly expresses surface T cell receptor molecules. The presence of two parallel lineages in the lpr thymus thus also provides insight into normal T cell development.

UI MeSH Term Description Entries
D008232 Lymphoproliferative Disorders Disorders characterized by proliferation of lymphoid tissue, general or unspecified. Duncan's Syndrome,X-Linked Lymphoproliferative Syndrome,Duncan Disease,Epstein-Barr Virus Infection, Familial Fatal,Epstein-Barr Virus-Induced Lymphoproliferative Disease In Males,Familial Fatal Epstein-Barr Infection,Immunodeficiency 5,Immunodeficiency, X-Linked Progressive Combined Variable,Lymphoproliferative Disease, X-Linked,Lymphoproliferative Syndrome, X-Linked, 1,Purtilo Syndrome,X-Linked Lymphoproliferative Disease,X-Linked Lymphoproliferative Disorder,Disease, Duncan,Disease, X-Linked Lymphoproliferative,Diseases, X-Linked Lymphoproliferative,Disorder, Lymphoproliferative,Disorder, X-Linked Lymphoproliferative,Disorders, Lymphoproliferative,Disorders, X-Linked Lymphoproliferative,Epstein Barr Virus Induced Lymphoproliferative Disease In Males,Epstein Barr Virus Infection, Familial Fatal,Familial Fatal Epstein Barr Infection,Immunodeficiency 5s,Immunodeficiency, X Linked Progressive Combined Variable,Lymphoproliferative Disease, X Linked,Lymphoproliferative Diseases, X-Linked,Lymphoproliferative Disorder,Lymphoproliferative Disorder, X-Linked,Lymphoproliferative Disorders, X-Linked,Lymphoproliferative Syndrome, X-Linked,Lymphoproliferative Syndromes, X-Linked,Purtilo Syndromes,Syndrome, Purtilo,Syndrome, X-Linked Lymphoproliferative,Syndromes, Purtilo,Syndromes, X-Linked Lymphoproliferative,X Linked Lymphoproliferative Disease,X Linked Lymphoproliferative Disorder,X Linked Lymphoproliferative Syndrome,X-Linked Lymphoproliferative Diseases,X-Linked Lymphoproliferative Disorders,X-Linked Lymphoproliferative Syndromes
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
D008817 Mice, Mutant Strains Mice bearing mutant genes which are phenotypically expressed in the animals. Mouse, Mutant Strain,Mutant Mouse Strain,Mutant Strain of Mouse,Mutant Strains of Mice,Mice Mutant Strain,Mice Mutant Strains,Mouse Mutant Strain,Mouse Mutant Strains,Mouse Strain, Mutant,Mouse Strains, Mutant,Mutant Mouse Strains,Mutant Strain Mouse,Mutant Strains Mice,Strain Mouse, Mutant,Strain, Mutant Mouse,Strains Mice, Mutant,Strains, Mutant Mouse
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
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
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
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
D001327 Autoimmune Diseases Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides. Autoimmune Disease,Disease, Autoimmune,Diseases, Autoimmune
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
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

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