Skip to main content
PMC home page
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
. 1977 Aug;74(8):3414–3418. doi: 10.1073/pnas.74.8.3414

Sequential stages of human T lymphocyte differentiation

Jean-Louis Touraine *,†, John W Hadden ‡, Robert A Good ‡
PMCID: PMC431586  PMID: 302943

Abstract

Induction of thymus-dependent lymphocyte (T cell) differentiation was performed in vitro with thymic factors as inducers. T cell precursors from human bone marrow first expressed surface differentiation antigens and then acquired the capacity to form rosettes with sheep erythrocytes. The latter marker could not be induced when cells with differentiation antigens had been eliminated. The proliferative responses to phytomitogens or to allogeneic stimuli appeared to be characteristics of later stages in differentiation that also can be induced or amplified by in vitro incubation of marrow cells or thymocytes with thymic factors. When phytomitogen-responsive cells from peripheral blood were inactivated in vitro, the allogeneic response was enhanced. Although these responses are acquired almost concomitantly, they are therefore envisioned to be characteristics of separate T cell subsets. After immunological reconstitution of patients, the T cell development in vivo involves a succession of differentiation events similar to that described above. Our experiments with mice, using similar methods, have also shown that graft-versus-host inducing capacity is a function of a cell population distinct from that which yields a proliferative response to in vitro stimulation by phytohemagglutinin. These results support our model of sequential differentiation of human prothymocytes into various subsets of mature T cells.

Keywords: prothymocyte, T cell markers, T cell functions, thymic factors

Full text

PDF
3414

Images in this article

3416Image
on p.3416

Selected References

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

  1. Bach J. F., Dardenne M., Goldstein A. L., Guha A., White A. Appearance of T-cell markers in bone marrow rosette-forming cells after incubation with thymosin, a thymic hormone. Proc Natl Acad Sci U S A. 1971 Nov;68(11):2734–2738. doi: 10.1073/pnas.68.11.2734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cantor H., Boyse E. A. Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J Exp Med. 1975 Jun 1;141(6):1390–1399. doi: 10.1084/jem.141.6.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carr M. C., Stites D. P., Fudenberg H. H. Dissociation of responses to phytohaemagglutinin and adult allogeneic lymphocytes in human foetal lymphoid tissues. Nat New Biol. 1973 Feb 28;241(113):279–281. doi: 10.1038/newbio241279a0. [DOI] [PubMed] [Google Scholar]
  4. Colley D. G., Wu A. Y., Waksman B. H. Cellular differentiation in the thymus. 3. Surface properties of rat thymus and lymph node cells separated on density gradients. J Exp Med. 1970 Dec 1;132(6):1107–1121. doi: 10.1084/jem.132.6.1107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Goldstein A. L., Guha A., Zatz M. M., Hardy M. A., White A. Purification and biological activity of thymosin, a hormone of the thymus gland. Proc Natl Acad Sci U S A. 1972 Jul;69(7):1800–1803. doi: 10.1073/pnas.69.7.1800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kisielow P., Hirst J. A., Shiku H., Beverley P. C., Hoffman M. K., Boyse E. A., Oettgen H. F. Ly antigens as markers for functionally distinct subpopulations of thymus-derived lymphocytes of the mouse. Nature. 1975 Jan 17;253(5488):219–220. doi: 10.1038/253219a0. [DOI] [PubMed] [Google Scholar]
  7. Komuro K., Boyse E. A. In-vitro demonstration of thymic hormone in the mouse by conversion of precursor cells into lymphocytes. Lancet. 1973 Apr 7;1(7806):740–743. doi: 10.1016/s0140-6736(73)92127-2. [DOI] [PubMed] [Google Scholar]
  8. Meuwissen H. J., Bach F. H., Hong R., Good R. A. Lymphocyte studies in congenital thymic dysplasia: The one-way stimulation test. J Pediatr. 1968 Feb;72(2):177–185. doi: 10.1016/s0022-3476(68)80306-3. [DOI] [PubMed] [Google Scholar]
  9. SIMONSEN M. Graft versus host reactions. Their natural history, and applicability as tools of research. Prog Allergy. 1962;6:349–467. [PubMed] [Google Scholar]
  10. Touraine J. L., Incefy G. S., Touraine F., Rho Y. M., Good R. A. Differentiation of human bone marrow cells into T lymphocytes by in vitro incubation with thymic extracts. Clin Exp Immunol. 1974 May;17(1):151–158. [PMC free article] [PubMed] [Google Scholar]
  11. Touraine J. L., Touraine F., Hadden J. W., Hadden E. M., Good R. A. 5-bromodeoxyuridine-light inactivation of human lymphocytes stimulated mitogens and allogeneic cells: evidence for distinct T-lymphocyte subsets. Int Arch Allergy Appl Immunol. 1976;52(1-4):105–117. doi: 10.1159/000231672. [DOI] [PubMed] [Google Scholar]
  12. Touraine J. L., Touraine F., Incefy G. S., Good R. A. Effect of thymic factors on the differentiation of human marrow cells into T-lympnocytes in vitro in normals and patients with immunodeficiencies. Ann N Y Acad Sci. 1975 Feb 28;249:335–342. doi: 10.1111/j.1749-6632.1975.tb29081.x. [DOI] [PubMed] [Google Scholar]
  13. Touraine J. L., Touraine F., Kiszkiss D. F., Choi Y. S., Good R. A. Heterologous specific antiserum for identification of human T lymphocytes. Clin Exp Immunol. 1974 Apr;16(4):503–520. [PMC free article] [PubMed] [Google Scholar]
  14. Vadas M. A., Miller J. F., McKenzie I. F., Chism S. E., Shen F. W., Boyse E. A., Gamble J. R., Whitelaw A. M. Ly and Ia antigen phenotypes of T cells involved in delayed-type hypersensitivity and in suppression. J Exp Med. 1976 Jul 1;144(1):10–19. doi: 10.1084/jem.144.1.10. [DOI] [PMC free article] [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