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Mature T cells generated from single thymic clones are phenotypically and functionally heterogeneous.
J Immunol. 1988 Sep 15; 141(6):1877-90.JI

Abstract

A limiting dilution system for cloning thymic CFU (CFUt) from murine bone marrow has been critically evaluated to test the clonal origin of the thymic colonies. Simultaneous limiting dilution transfer of three populations of bone marrow, each expressing a unique allelic cell surface determinant, resulted in independent segregation of donor-derived thymocyte populations within groups of recipient mice. Statistical analysis of the data allowed an estimate of 1 CFUt/3.3 x 10(4) i.v. transferred bone marrow cells. A pulse-chase experiment was utilized to establish whether CFUt seed directly to the thymus, or whether thymic seeding is secondary to extra-thymic engraftment. The results supported the conclusion that bone marrow CFUt utilize a specific interaction with thymic blood vessel endothelial cells to recognize and enter the thymus, and that this seeding occurs within 4 h of i.v. infusion. A kinetic analysis of emigration of the CFUt progeny into the peripheral blood revealed that, in most cases, an early wave of predominantly CD4+ CD8- lymphocytes emerges from the thymus approximately 4 wk after radiation and reconstitution. In a few cases, the first progeny of CFUt to emerge from the thymus were predominantly CD4- CD8+. Commitment of CFUt to TCR beta-chain rearrangements was assessed by quantitating expression of the V beta 8 family of TCR V region genes. Although some clones expressed a significantly higher or lower percentage of V beta 8+ cells, these differences were not stable with time. Thus, CFUt do not undergo absolute commitment to cell surface phenotype of TCR rearrangement, as reflected by the phenotypes of their progeny. Clones of mature peripheral progeny of CFUt could be expanded in culture in the presence of mitogen and growth factors; approximately 30 to 50% of proliferating clones could mediate cytotoxicity in a lectin-dependent assay, further indicating that CFUt are not absolutely committed to a particular T cell function.

Authors+Show Affiliations

Department of Pathology, Stanford University School of Medicine, CA 94305.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

3262643

Citation

Spangrude, G J., and I L. Weissman. "Mature T Cells Generated From Single Thymic Clones Are Phenotypically and Functionally Heterogeneous." Journal of Immunology (Baltimore, Md. : 1950), vol. 141, no. 6, 1988, pp. 1877-90.
Spangrude GJ, Weissman IL. Mature T cells generated from single thymic clones are phenotypically and functionally heterogeneous. J Immunol. 1988;141(6):1877-90.
Spangrude, G. J., & Weissman, I. L. (1988). Mature T cells generated from single thymic clones are phenotypically and functionally heterogeneous. Journal of Immunology (Baltimore, Md. : 1950), 141(6), 1877-90.
Spangrude GJ, Weissman IL. Mature T Cells Generated From Single Thymic Clones Are Phenotypically and Functionally Heterogeneous. J Immunol. 1988 Sep 15;141(6):1877-90. PubMed PMID: 3262643.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mature T cells generated from single thymic clones are phenotypically and functionally heterogeneous. AU - Spangrude,G J, AU - Weissman,I L, PY - 1988/9/15/pubmed PY - 1988/9/15/medline PY - 1988/9/15/entrez SP - 1877 EP - 90 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 141 IS - 6 N2 - A limiting dilution system for cloning thymic CFU (CFUt) from murine bone marrow has been critically evaluated to test the clonal origin of the thymic colonies. Simultaneous limiting dilution transfer of three populations of bone marrow, each expressing a unique allelic cell surface determinant, resulted in independent segregation of donor-derived thymocyte populations within groups of recipient mice. Statistical analysis of the data allowed an estimate of 1 CFUt/3.3 x 10(4) i.v. transferred bone marrow cells. A pulse-chase experiment was utilized to establish whether CFUt seed directly to the thymus, or whether thymic seeding is secondary to extra-thymic engraftment. The results supported the conclusion that bone marrow CFUt utilize a specific interaction with thymic blood vessel endothelial cells to recognize and enter the thymus, and that this seeding occurs within 4 h of i.v. infusion. A kinetic analysis of emigration of the CFUt progeny into the peripheral blood revealed that, in most cases, an early wave of predominantly CD4+ CD8- lymphocytes emerges from the thymus approximately 4 wk after radiation and reconstitution. In a few cases, the first progeny of CFUt to emerge from the thymus were predominantly CD4- CD8+. Commitment of CFUt to TCR beta-chain rearrangements was assessed by quantitating expression of the V beta 8 family of TCR V region genes. Although some clones expressed a significantly higher or lower percentage of V beta 8+ cells, these differences were not stable with time. Thus, CFUt do not undergo absolute commitment to cell surface phenotype of TCR rearrangement, as reflected by the phenotypes of their progeny. Clones of mature peripheral progeny of CFUt could be expanded in culture in the presence of mitogen and growth factors; approximately 30 to 50% of proliferating clones could mediate cytotoxicity in a lectin-dependent assay, further indicating that CFUt are not absolutely committed to a particular T cell function. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/3262643/Mature_T_cells_generated_from_single_thymic_clones_are_phenotypically_and_functionally_heterogeneous_ DB - PRIME DP - Unbound Medicine ER -