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Changes in inducibility of IL-2 receptor alpha-chain and T cell-receptor expression during thymocyte differentiation in the mouse.
J Immunol. 1989 Jun 15; 142(12):4121-30.JI

Abstract

Within the thymus, developing T cells must acquire the competence to respond to appropriate signals by inducing the expression of genes required for immunologic function; one such gene encodes the 55-kDa-chain of the IL-2R (IL-2R alpha). Previously, we showed that most cortical-type thymocytes lack the competence to make this particular response, while most medullary-type cells respond like mature T lymphocytes. The noninducibility of cortical-type cells was striking, because most of their presumed precursors were inducible. To test the relationship between this apparent loss of competence and the positive and negative selection processes that may occur in the thymic cortex, we have assayed the inducibility of thymocyte populations, staged carefully with respect to their expression of TCR. Using size fractionation to enrich for dividing cells, we concentrated and thereby revealed defined developmental intermediates. We report that, although CD4+CD8- thymocytes behave as mature T cells, a significant fraction of CD4-CD8+ cells are noninducible. These noninducible thymocytes are dividing cells, which appear to be in a major developmental continuum between CD4-CD8- blasts and CD4+CD8+ blasts. Furthermore, the noninducible blasts as yet lack surface TCR expression. We also demonstrate the functional similarity of these CD4-CD8+ cells to a major subset of dividing CD4-CD8- precursor cells, which appear to have lost IL-2R alpha expression. These results suggest that precursors of cortical thymocytes lose competence to be induced to express IL-2R alpha several stages before their acquisition of cell-surface TCR complexes. The implications of this characterization are discussed in terms of the possible relationships between IL-2R alpha gene regulation and intrathymic fate determination.

Authors+Show Affiliations

Division of Biology, California Institute of Technology, Pasadena 91125.No affiliation info availableNo 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

2498427

Citation

Boyer, P D., et al. "Changes in Inducibility of IL-2 Receptor Alpha-chain and T Cell-receptor Expression During Thymocyte Differentiation in the Mouse." Journal of Immunology (Baltimore, Md. : 1950), vol. 142, no. 12, 1989, pp. 4121-30.
Boyer PD, Diamond RA, Rothenberg EV. Changes in inducibility of IL-2 receptor alpha-chain and T cell-receptor expression during thymocyte differentiation in the mouse. J Immunol. 1989;142(12):4121-30.
Boyer, P. D., Diamond, R. A., & Rothenberg, E. V. (1989). Changes in inducibility of IL-2 receptor alpha-chain and T cell-receptor expression during thymocyte differentiation in the mouse. Journal of Immunology (Baltimore, Md. : 1950), 142(12), 4121-30.
Boyer PD, Diamond RA, Rothenberg EV. Changes in Inducibility of IL-2 Receptor Alpha-chain and T Cell-receptor Expression During Thymocyte Differentiation in the Mouse. J Immunol. 1989 Jun 15;142(12):4121-30. PubMed PMID: 2498427.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Changes in inducibility of IL-2 receptor alpha-chain and T cell-receptor expression during thymocyte differentiation in the mouse. AU - Boyer,P D, AU - Diamond,R A, AU - Rothenberg,E V, PY - 1989/6/15/pubmed PY - 1989/6/15/medline PY - 1989/6/15/entrez SP - 4121 EP - 30 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 142 IS - 12 N2 - Within the thymus, developing T cells must acquire the competence to respond to appropriate signals by inducing the expression of genes required for immunologic function; one such gene encodes the 55-kDa-chain of the IL-2R (IL-2R alpha). Previously, we showed that most cortical-type thymocytes lack the competence to make this particular response, while most medullary-type cells respond like mature T lymphocytes. The noninducibility of cortical-type cells was striking, because most of their presumed precursors were inducible. To test the relationship between this apparent loss of competence and the positive and negative selection processes that may occur in the thymic cortex, we have assayed the inducibility of thymocyte populations, staged carefully with respect to their expression of TCR. Using size fractionation to enrich for dividing cells, we concentrated and thereby revealed defined developmental intermediates. We report that, although CD4+CD8- thymocytes behave as mature T cells, a significant fraction of CD4-CD8+ cells are noninducible. These noninducible thymocytes are dividing cells, which appear to be in a major developmental continuum between CD4-CD8- blasts and CD4+CD8+ blasts. Furthermore, the noninducible blasts as yet lack surface TCR expression. We also demonstrate the functional similarity of these CD4-CD8+ cells to a major subset of dividing CD4-CD8- precursor cells, which appear to have lost IL-2R alpha expression. These results suggest that precursors of cortical thymocytes lose competence to be induced to express IL-2R alpha several stages before their acquisition of cell-surface TCR complexes. The implications of this characterization are discussed in terms of the possible relationships between IL-2R alpha gene regulation and intrathymic fate determination. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/2498427/Changes_in_inducibility_of_IL_2_receptor_alpha_chain_and_T_cell_receptor_expression_during_thymocyte_differentiation_in_the_mouse_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=2498427 DB - PRIME DP - Unbound Medicine ER -