Abstract
Precursors of all T-lineage cells are found in the population of thymocytes that lacks the CD4 and CD8 surface markers. These "double-negative" thymocytes are heterogeneous and can be divided into discrete subpopulations based on their expression of other surface markers. We have determined the relative maturity of these subpopulations based on the extent of rearrangement and expression of their T-cell receptor genes, their cell cycle status, and their thymus reconstitution capacity. Within the subpopulation of double negatives expressing high levels of the heat-stable antigen, the additional markers phagocytic glycoprotein 1 (Pgp-1) and interleukin 2 receptor (IL-2R) can be used to define the sequence IL-2R- Pgp-1+----IL-2R+ Pgp-1-----IL-2R- Pgp-1-, which occurs before the expression of CD4 and CD8. Transient expression of the IL-2R marks an important developmental point in the sequence just prior to a burst of cell proliferation and a loss of thymus reconstitution ability. The earliest cells in this sequence are already partially rearranged for genes in the C beta 1 region. IL-2R expression marks a second wave of T-cell antigen receptor of beta-chain gene rearrangement and the initiation of T-cell antigen receptor alpha- and beta-chain gene expression.
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Selected References
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- Bluestone J. A., Pardoll D., Sharrow S. O., Fowlkes B. J. Characterization of murine thymocytes with CD3-associated T-cell receptor structures. Nature. 1987 Mar 5;326(6108):82–84. doi: 10.1038/326082a0. [DOI] [PubMed] [Google Scholar]
- Budd R. C., Miescher G. C., Howe R. C., Lees R. K., Bron C., MacDonald H. R. Developmentally regulated expression of T cell receptor beta chain variable domains in immature thymocytes. J Exp Med. 1987 Aug 1;166(2):577–582. doi: 10.1084/jem.166.2.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cook W. D., Balaton A. M. T-cell receptor and immunoglobulin genes are rearranged together in Abelson virus-transformed pre-B and pre-T cells. Mol Cell Biol. 1987 Jan;7(1):266–272. doi: 10.1128/mcb.7.1.266. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crispe I. N., Moore M. W., Husmann L. A., Smith L., Bevan M. J., Shimonkevitz R. P. Differentiation potential of subsets of CD4-8- thymocytes. Nature. 1987 Sep 24;329(6137):336–339. doi: 10.1038/329336a0. [DOI] [PubMed] [Google Scholar]
- Ewing T., Egerton M., Wilson A., Scollay R., Shortman K. Subpopulations of CD4- CD8- murine thymocytes: differences in proliferation rate in vivo and proliferative responses in vitro. Eur J Immunol. 1988 Feb;18(2):261–268. doi: 10.1002/eji.1830180213. [DOI] [PubMed] [Google Scholar]
- Fowlkes B. J., Kruisbeek A. M., Ton-That H., Weston M. A., Coligan J. E., Schwartz R. H., Pardoll D. M. A novel population of T-cell receptor alpha beta-bearing thymocytes which predominantly expresses a single V beta gene family. Nature. 1987 Sep 17;329(6136):251–254. doi: 10.1038/329251a0. [DOI] [PubMed] [Google Scholar]
- Fowlkes B. J., Schwartz R. H., Pardoll D. M. Deletion of self-reactive thymocytes occurs at a CD4+8+ precursor stage. Nature. 1988 Aug 18;334(6183):620–623. doi: 10.1038/334620a0. [DOI] [PubMed] [Google Scholar]
- Hedrick S. M., Nielsen E. A., Kavaler J., Cohen D. I., Davis M. M. Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins. Nature. 1984 Mar 8;308(5955):153–158. doi: 10.1038/308153a0. [DOI] [PubMed] [Google Scholar]
- Hyman R., Lesley J., Schulte R., Trotter J. Progenitor cells in the thymus: most thymus-homing progenitor cells in the adult mouse thymus bear Pgp-1 glycoprotein but not interleukin-2 receptor on their cell surface. Cell Immunol. 1986 Sep;101(2):320–327. doi: 10.1016/0008-8749(86)90145-0. [DOI] [PubMed] [Google Scholar]
- Kappler J. W., Roehm N., Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987 Apr 24;49(2):273–280. doi: 10.1016/0092-8674(87)90568-x. [DOI] [PubMed] [Google Scholar]
- Kisielow P., Blüthmann H., Staerz U. D., Steinmetz M., von Boehmer H. Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature. 1988 Jun 23;333(6175):742–746. doi: 10.1038/333742a0. [DOI] [PubMed] [Google Scholar]
- MacDonald H. R., Howe R. C., Pedrazzini T., Lees R. K., Budd R. C., Schneider R., Liao N. S., Zinkernagel R. M., Louis J. A., Raulet D. H. T-cell lineages, repertoire selection and tolerance induction. Immunol Rev. 1988 Aug;104:157–182. doi: 10.1111/j.1600-065x.1988.tb00762.x. [DOI] [PubMed] [Google Scholar]
- McPhee D., Pye J., Shortman K. The differentiation of T lymphocytes. V. Evidence for intrathymic death of most thymocytes. Thymus. 1979 Nov;1(3):151–162. [PubMed] [Google Scholar]
- Miescher G. C., Howe R. C., Lees R. K., MacDonald H. R. CD3-associated alpha/beta and gamma/delta heterodimeric receptors are expressed by distinct populations of CD4- CD8- thymocytes. J Immunol. 1988 Mar 15;140(6):1779–1782. [PubMed] [Google Scholar]
- Nakano N., Hardy R. R., Kishimoto T. Identification of intrathymic T progenitor cells by expression of Thy-1, IL2 receptor and CD3. Eur J Immunol. 1987 Nov;17(11):1567–1571. doi: 10.1002/eji.1830171107. [DOI] [PubMed] [Google Scholar]
- Pearse M. J., Wu L. Preparation of both DNA and RNA for hybridization analysis from limiting quantities of lymphoid cells. Immunol Lett. 1988 Jul;18(3):219–223. doi: 10.1016/0165-2478(88)90022-3. [DOI] [PubMed] [Google Scholar]
- Pearse M., Gallagher P., Wilson A., Wu L., Fisicaro N., Miller J. F., Scollay R., Shortman K. Molecular characterization of T-cell antigen receptor expression by subsets of CD4- CD8- murine thymocytes. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6082–6086. doi: 10.1073/pnas.85.16.6082. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Raulet D. H. Expression and function of interleukin-2 receptors on immature thymocytes. Nature. 1985 Mar 7;314(6006):101–103. doi: 10.1038/314101a0. [DOI] [PubMed] [Google Scholar]
- Scollay R. G., Butcher E. C., Weissman I. L. Thymus cell migration. Quantitative aspects of cellular traffic from the thymus to the periphery in mice. Eur J Immunol. 1980 Mar;10(3):210–218. doi: 10.1002/eji.1830100310. [DOI] [PubMed] [Google Scholar]
- Scollay R., Shortman K. Identification of early stages of T lymphocyte development in the thymus cortex and medulla. J Immunol. 1985 Jun;134(6):3632–3642. [PubMed] [Google Scholar]
- Scollay R., Wilson A., D'Amico A., Kelly K., Egerton M., Pearse M., Wu L., Shortman K. Developmental status and reconstitution potential of subpopulations of murine thymocytes. Immunol Rev. 1988 Aug;104:81–120. doi: 10.1111/j.1600-065x.1988.tb00760.x. [DOI] [PubMed] [Google Scholar]
- Shimonkevitz R. P., Husmann L. A., Bevan M. J., Crispe I. N. Transient expression of IL-2 receptor precedes the differentiation of immature thymocytes. Nature. 1987 Sep 10;329(6135):157–159. doi: 10.1038/329157a0. [DOI] [PubMed] [Google Scholar]
- Shortman K., Wilson A., Egerton M., Pearse M., Scollay R. Immature CD4- CD8+ murine thymocytes. Cell Immunol. 1988 May;113(2):462–479. doi: 10.1016/0008-8749(88)90042-1. [DOI] [PubMed] [Google Scholar]
- Spangrude G. J., Heimfeld S., Weissman I. L. Purification and characterization of mouse hematopoietic stem cells. Science. 1988 Jul 1;241(4861):58–62. doi: 10.1126/science.2898810. [DOI] [PubMed] [Google Scholar]
- Taylor I. W. A rapid single step staining technique for DNA analysis by flow microfluorimetry. J Histochem Cytochem. 1980 Sep;28(9):1021–1024. doi: 10.1177/28.9.6157714. [DOI] [PubMed] [Google Scholar]
- Trowbridge I. S., Lesley J., Trotter J., Hyman R. Thymocyte subpopulation enriched for progenitors with an unrearranged T-cell receptor beta-chain gene. Nature. 1985 Jun 20;315(6021):666–669. doi: 10.1038/315666a0. [DOI] [PubMed] [Google Scholar]
- Wilson A., D'Amico A., Ewing T., Scollay R., Shortman K. Subpopulations of early thymocytes. A cross-correlation flow cytometric analysis of adult mouse Ly-2-L3T4-(CD8-CD4-) thymocytes using eight different surface markers. J Immunol. 1988 Mar 1;140(5):1461–1469. [PubMed] [Google Scholar]
- Wilson A., Ewing T., Owens T., Scollay R., Shortman K. T cell antigen receptor expression by subsets of Ly-2-L3T4- (CD8-CD4-) thymocytes. J Immunol. 1988 Mar 1;140(5):1470–1476. [PubMed] [Google Scholar]
- Zauderer M., Iwamoto A., Mak T. W. Gamma gene rearrangement and expression in autoreactive helper T cells. J Exp Med. 1986 May 1;163(5):1314–1318. doi: 10.1084/jem.163.5.1314. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de la Hera A., Toribio M. L., Marquez C., Martinez C. Interleukin 2 promotes growth and cytolytic activity in human T3+4-8- thymocytes. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6268–6271. doi: 10.1073/pnas.82.18.6268. [DOI] [PMC free article] [PubMed] [Google Scholar]
- von Boehmer H., Crisanti A., Kisielow P., Haas W. Absence of growth by most receptor-expressing fetal thymocytes in the presence of interleukin-2. Nature. 1985 Apr 11;314(6011):539–540. doi: 10.1038/314539a0. [DOI] [PubMed] [Google Scholar]