Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1980 Mar;77(3):1588–1592. doi: 10.1073/pnas.77.3.1588

Discrete stages of human intrathymic differentiation: Analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage

Ellis L Reinherz *, Patrick C Kung , Gideon Goldstein , Raphael H Levey , Stuart F Schlossman *
PMCID: PMC348542  PMID: 6966400

Abstract

A series of monoclonal antibodies was used to define three discrete stages of human intrathymic T-cell differentiation. The earliest stage was confined to <10% of thymocytes, which were·reactive with both OKT9 and OKT10. Subsequently, approximately 70% of human thymocytes acquired a thymocyte-restricted antigen, OKT6, lost OKT9 antigen, and expressed reactivity with OKT4 and OKT5. These last two monoclonal antibodies were previously shown to define inducer (helper) and cytotoxic/suppressor populations, respectively, in peripheral blood. The OKT4+, OKT5+, OKT6+ “common” thymocyte population represents the majority of thymocytes and accounts for more than 70% of thymocytes. With further maturation, thymocytes lose OKT6 reactivity, segregate into OKT4+ and OKT5+ subsets, and acquire reactivity with OKT3 (and OKT1). This latter stage corresponds to the more functionally mature subset. The possible relationship of acute lymphoblastic leukemia of T-cell lineage to these proposed stages of intrathymic differentiation was determined. Analysis of 25 tumor populations showed that 21 could be related to one or another differentiative stage. The majority (15/21) were derived from an early thymocyte or prothymocyte subpopulation, 5/25 were derived from a common thymocyte subpopulation, and 1/25 was derived from a mature (OKT3+) subpopulation. These data suggest that is it now possible to define stages of T-cell differentiation that can be related to T-cell malignancies in humans.

Keywords: T-cell ontogeny, human thymus, hybridoma

Full text

PDF
1588

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cantor H., Boyse E. A. Functional subclasses of T-lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J Exp Med. 1975 Jun 1;141(6):1376–1389. doi: 10.1084/jem.141.6.1376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cantor H., Shen F. W., Boyse E. A. Separation of helper T cells from suppressor T cells expressing different Ly components. II. Activation by antigen: after immunization, antigen-specific suppressor and helper activities are mediated by distinct T-cell subclasses. J Exp Med. 1976 Jun 1;143(6):1391–1340. doi: 10.1084/jem.143.6.1391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Evans R. L., Lazarus H., Penta A. C., Schlossman S. F. Two functionally distinct subpopulations of human T cells that collaborate in the generation of cytotoxic cells responsible for cell-mediated lympholysis. J Immunol. 1978 Apr;120(4):1423–1428. [PubMed] [Google Scholar]
  4. Konda S., Stockert E., Smith R. T. Immunologic properties of mouse thymus cells: membrane antigen patterns associated with various cell subpopulations. Cell Immunol. 1973 May;7(2):275–289. doi: 10.1016/0008-8749(73)90250-5. [DOI] [PubMed] [Google Scholar]
  5. Kung P., Goldstein G., Reinherz E. L., Schlossman S. F. Monoclonal antibodies defining distinctive human T cell surface antigens. Science. 1979 Oct 19;206(4416):347–349. doi: 10.1126/science.314668. [DOI] [PubMed] [Google Scholar]
  6. McMichael A. J., Pilch J. R., Galfré G., Mason D. Y., Fabre J. W., Milstein C. A human thymocyte antigen defined by a hybrid myeloma monoclonal antibody. Eur J Immunol. 1979 Mar;9(3):205–210. doi: 10.1002/eji.1830090307. [DOI] [PubMed] [Google Scholar]
  7. Moore M. A., Owen J. J. Experimental studies on the development of the thymus. J Exp Med. 1967 Oct 1;126(4):715–726. doi: 10.1084/jem.126.4.715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Owen J. J., Raff M. C. Studies on the differentiation of thymus-derived lymphocytes. J Exp Med. 1970 Dec 1;132(6):1216–1232. doi: 10.1084/jem.132.6.1216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Owen J. J., Ritter M. A. Tissue interaction in the development of thymus lymphocytes. J Exp Med. 1969 Feb 1;129(2):431–442. doi: 10.1084/jem.129.2.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Raff M. C. Surface antigenic markers for distinguishing T and B lymphocytes in mice. Transplant Rev. 1971;6:52–80. doi: 10.1111/j.1600-065x.1971.tb00459.x. [DOI] [PubMed] [Google Scholar]
  11. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. A monoclonal antibody with selective reactivity with functionally mature human thymocytes and all peripheral human T cells. J Immunol. 1979 Sep;123(3):1312–1317. [PubMed] [Google Scholar]
  12. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. Further characterization of the human inducer T cell subset defined by monoclonal antibody. J Immunol. 1979 Dec;123(6):2894–2896. [PubMed] [Google Scholar]
  13. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci U S A. 1979 Aug;76(8):4061–4065. doi: 10.1073/pnas.76.8.4061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Reinherz E. L., Kung P. C., Pesando J. M., Ritz J., Goldstein G., Schlossman S. F. Ia determinants on human T-cell subsets defined by monoclonal antibody. Activation stimuli required for expression. J Exp Med. 1979 Dec 1;150(6):1472–1482. doi: 10.1084/jem.150.6.1472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Reinherz E. L., Nadler L. M., Sallan S. E., Schlossman S. F. Subset derivation of T-cell acute lymphoblastic leukemia in man. J Clin Invest. 1979 Aug;64(2):392–397. doi: 10.1172/JCI109474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Reinherz E. L., Parkman R., Rappeport J., Rosen F. S., Schlossman S. F. Aberrations of suppressor T cells in human graft-versus-host disease. N Engl J Med. 1979 May 10;300(19):1061–1068. doi: 10.1056/NEJM197905103001901. [DOI] [PubMed] [Google Scholar]
  17. Reinherz E. L., Rubinstein A., Geha R. S., Strelkauskas A. J., Rosen F. S., Schlossman S. F. Abnormalities of immunoregulatory T cells in disorders of immune function. N Engl J Med. 1979 Nov 8;301(19):1018–1022. doi: 10.1056/NEJM197911083011902. [DOI] [PubMed] [Google Scholar]
  18. Reinherz E. L., Schlossman S. F. Con A-inducible suppression of MLC: evidence for mediation by the TH2 + T cell subset in man. J Immunol. 1979 Apr;122(4):1335–1341. [PubMed] [Google Scholar]
  19. Reinherz E. L., Strelkauskas A. J., O'Brien C., Schlossman S. F. Phenotypic and functional distinctions between the TH2+ and JRA+ T cell subsets in man. J Immunol. 1979 Jul;123(1):83–86. [PubMed] [Google Scholar]
  20. Schlossman S. F., Chess L., Humphreys R. E., Strominger J. L. Distribution of Ia-like molecules on the surface of normal and leukemic human cells. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1288–1292. doi: 10.1073/pnas.73.4.1288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Stutman O., Good R. A. Immunocompetence of embryonic hemopoietic cells after traffic to thymus. Transplant Proc. 1971 Mar;3(1):923–925. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES