Home LiteratureArticle Details
PMID: 3081905 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Early precursor thymocytes can produce interleukin 2 upon stimulation with calcium ionophore and phorbol ester.

Lugo JP, Krishnan SN, Sailor RD, Rothenberg EV

Abstract

T-cell precursors were stimulated with a conventional T-cell mitogen or with the calcium ionophore A23187 in order to determine whether pre-T cells acquire the ability to produce interleukin 2 (IL-2) before they acquire the ability to respond to antigen or mitogenic lectins. Immature T cells were obtained by eliminating mouse thymocytes that expressed the Lyt2 and L3T4 cell surface proteins. The remaining Lyt2-, L3T4- cells were stimulated for IL-2 production by using concanavalin A (Con A) or A23187, together with phorbol 12-myristate 13-acetate (PMA). We found that these "double-negative" thymocytes were unresponsive to Con A plus PMA but produced substantial amounts of IL-2 when stimulated with A23187 plus PMA. In contrast, both stimulation regimens induced more mature T-lymphocyte populations to produce IL-2. This implies that developing T cells acquire the ability to make IL-2 upon induction before they acquire the ability to be triggered by Con A. Day-15 fetal and cortical thymocytes were also tested for their ability to make IL-2. Both populations failed to synthesize this growth factor, even when stimulated with A23187 and PMA. For cortical thymocytes, this result, together with the finding that A23187 plus PMA fails to activate these cells, suggests that this population is immunologically inert rather than immature. On the other hand, the inability of day-15 fetal thymocytes to produce IL-2 indicates that these T-cell precursors are developmentally distinct from adult Lyt2-, L3T4- thymocytes, which they phenotypically resemble.

MeSH Terms
Animals Antibodies, Monoclonal/immunology Antigens, Ly/analysis Calcimycin/pharmacology Cell Differentiation Concanavalin A/pharmacology Flow Cytometry Hematopoietic Stem Cells/drug effects,metabolism Interleukin-2/biosynthesis Lymphocyte Activation/drug effects Mice Mice, Inbred C57BL Phorbols/pharmacology T-Lymphocytes/drug effects,metabolism Tetradecanoylphorbol Acetate/pharmacology Thymus Gland/cytology,embryology
Chemicals
Antibodies, Monoclonal Antigens, Ly Interleukin-2 Phorbols Concanavalin A Calcimycin Tetradecanoylphorbol Acetate
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lugo J P
Krishnan S N
Sailor R D
Rothenberg E V
References (34)
34 references, click to expand
  1. Clonotypic structures involved in antigen-specific human T cell function. Relationship to the T3 molecular complex.
    J Exp Med. 1983 Feb 1;157(2):705-19 PMID: 6185617
  2. Differentiation and cell division in the mammalian thymus.
    Dev Biol. 1985 Nov;112(1):1-17 PMID: 3932107
  3. The major histocompatibility complex-restricted antigen receptor on T cells in mouse and man: identification of constant and variable peptides.
    Cell. 1983 Nov;35(1):295-302 PMID: 6605199
  4. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule.
    J Immunol. 1983 Nov;131(5):2445-51 PMID: 6415170
  5. Precursors of T cell growth factor producing cells in the thymus: ontogeny, frequency, and quantitative recovery in a subpopulation of phenotypically mature thymocytes defined by monoclonal antibody GK-1.5.
    J Exp Med. 1983 Nov 1;158(5):1654-71 PMID: 6195289
  6. Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences.
    Nature. 1984 Jun 28-Jul 4;309(5971):757-62 PMID: 6330561
  7. Role of T3 surface molecules in human T-cell activation: T3-dependent activation results in an increase in cytoplasmic free calcium.
    Proc Natl Acad Sci U S A. 1984 Jul;81(13):4169-73 PMID: 6234599
  8. A homing receptor-bearing cortical thymocyte subset: implications for thymus cell migration and the nature of cortisone-resistant thymocytes.
    Cell. 1984 Aug;38(1):89-99 PMID: 6432340
  9. The major histocompatibility complex-restricted antigen receptor on T cells: distribution on thymus and peripheral T cells.
    Cell. 1984 Sep;38(2):577-84 PMID: 6331891
  10. The murine IL 2 receptor. I. Monoclonal antibodies that define distinct functional epitopes on activated T cells and react with activated B cells.
    J Immunol. 1984 Oct;133(4):1970-5 PMID: 6206144
  11. High-level secretion of interleukin 2 by a subset of proliferating thymic lymphoblasts.
    J Immunol. 1984 Oct;133(4):1983-91 PMID: 6332143
  12. T-Cell lymphoma model for the analysis of interleukin 1-mediated T-cell activation.
    Proc Natl Acad Sci U S A. 1981 Feb;78(2):1133-7 PMID: 6785748
  13. Phenotypic and functional properties of murine thymocytes. I. Precursors of cytolytic T lymphocytes and interleukin 2-producing cells are all contained within a subpopulation of "mature" thymocytes as analyzed by monoclonal antibodies and flow microfluorometry.
    J Exp Med. 1982 Feb 1;155(2):358-79 PMID: 6120202
  14. T-cell mitogens cause early changes in cytoplasmic free Ca2+ and membrane potential in lymphocytes.
    Nature. 1982 Jan 7;295(5844):68-71 PMID: 6799829
  15. The functional capacity of thymus subpopulations: limit-dilution analysis of all precursors of cytotoxic lymphocytes and of all T cells capable of proliferation in subpopulations separated by the use of peanut agglutinin.
    J Immunol. 1982 Jul;129(1):18-24 PMID: 6211480
  16. Monoclonal antibodies against rat immunoglobulin kappa chains.
    Hybridoma. 1982;1(2):125-31 PMID: 6821397
  17. Structure, organization, and somatic rearrangement of T cell gamma genes.
    Cell. 1985 Feb;40(2):259-69 PMID: 3917858
  18. Increase in cytosolic free calcium concentration is an intracellular messenger for the production of interleukin 2 but not for expression of the interleukin 2 receptor.
    J Immunol. 1985 Mar;134(3):1640-3 PMID: 3918108
  19. Early steps of lymphocyte activation bypassed by synergy between calcium ionophores and phorbol ester.
    Nature. 1985 Jan 24-30;313(6000):318-20 PMID: 3918270
  20. Ontogeny of the T-cell antigen receptor within the thymus.
    Nature. 1985 Feb 14-20;313(6003):592-5 PMID: 3871511
  21. Transmembrane signalling by the T cell antigen receptor. Perturbation of the T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores.
    J Exp Med. 1985 Mar 1;161(3):446-56 PMID: 3919143
  22. Expression and function of interleukin-2 receptors on immature thymocytes.
    Nature. 1985 Mar 7-13;314(6006):101-3 PMID: 3919309
  23. Developmental regulation of T-cell receptor gene expression.
    Nature. 1985 Mar 7-13;314(6006):103-7 PMID: 2983227
  24. Expression of interleukin-2 receptors as a differentiation marker on intrathymic stem cells.
    Nature. 1985 Mar 7-13;314(6006):98-100 PMID: 3919312
  25. Cell surface antigen expression on thymocytes: development and phenotypic differentiation of intrathymic subsets.
    Immunol Rev. 1984 Dec;82:141-73 PMID: 6442264
  26. Identification of early stages of T lymphocyte development in the thymus cortex and medulla.
    J Immunol. 1985 Jun;134(6):3632-42 PMID: 3886788
  27. Distinction between antigen receptor and IL 2 receptor triggering events in the activation of alloreactive T cell clones with calcium ionophore and phorbol ester.
    J Immunol. 1985 Jun;134(6):3649-55 PMID: 3921610
  28. Proliferation of thymic stem cells with and without receptors for interleukin 2. Implications for intrathymic antigen recognition.
    J Exp Med. 1985 May 1;161(5):1048-62 PMID: 3921650
  29. Absence of growth by most receptor-expressing fetal thymocytes in the presence of interleukin-2.
    Nature. 1985 Apr 11-17;314(6011):539-40 PMID: 2859525
  30. Rearrangement of T-cell receptor beta-chain genes during T-cell development.
    Proc Natl Acad Sci U S A. 1985 May;82(9):2925-9 PMID: 3873070
  31. Expression of T-cell antigen receptor genes during fetal development in the thymus.
    Nature. 1985 May 16-22;315(6016):232-3 PMID: 3873615
  32. Thymocyte subpopulation enriched for progenitors with an unrearranged T-cell receptor beta-chain gene.
    Nature. 1985 Jun 20-26;315(6021):666-9 PMID: 3874369
  33. Expression of genes of the T-cell antigen receptor complex in precursor thymocytes.
    Nature. 1985 Jun 27-Jul 3;315(6022):765-8 PMID: 4010781
  34. Differentiation in vitro of Lyt 2+ thymocytes from embryonic Lyt 2- precursors.
    Nature. 1983 May 19-25;303(5914):248-50 PMID: 6601775
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1986-03-00
Pages
1862-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC323184
Subset
IM
Grants
NIAID NIH HHS · AI19752 · United States
NCI NIH HHS · CA32911 · United States
NCI NIH HHS · CA39605 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]