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. 1978 Sep;75(9):4474–4478. doi: 10.1073/pnas.75.9.4474

Amplification of the proliferative response to alloantigen by a factor present in an extract of syngeneic thymic lymphoid cells.

P W Wright, S M Loop
PMCID: PMC336138  PMID: 279929

Abstract

A synergistic interaction in the proliferative response to alloantigen has been previously noted when intact thymus cells are cultured with post-thymic (peripheral) lymphoid cells. In the present study, a factor extracted from the thymus has been shown to similarly enhance the reactivity of syngeneic lymph node cells and thus to retain the amplifier activity of intact thymus cells. The factor has no effect on lymphoid cell proliferation in the absence of alloantigen. Cells with amplifier activity are found in highest concentration in the thymus but also may be detected in spleen cells that are nonadherent to nylon wool. The factor is shown in these experiments to be derived from thymic lymphoid cells and to act primarily upon post-thymic (peripheral) lymphoid cells. As such, this factor appears to be distinct from various other thymus factors that have been localized to thymic reticuloepithelial elements and that are thought to effect predominantly the differentiation of T-cell precursors.

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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. Bach J. F., Dardenne M., Pleau J. M., Bach M. A. Isolation, biochemical characteristics, and biological activity of a circulating thymic hormone in the mouse and in the human. Ann N Y Acad Sci. 1975 Feb 28;249:186–210. doi: 10.1111/j.1749-6632.1975.tb29068.x. [DOI] [PubMed] [Google Scholar]
  3. Balch C. M., Feldman J. D. Thymus-dependent (T) lymphocytes in the rat. J Immunol. 1974 Jan;112(1):79–86. [PubMed] [Google Scholar]
  4. Berlinger N. T., Lopez C., Good R. A. Facilitation or attenuation of mixed leukocyte culture responsiveness by adherent cells. Nature. 1976 Mar 11;260(5547):145–146. doi: 10.1038/260145a0. [DOI] [PubMed] [Google Scholar]
  5. Cantor H., Asofsky R. Synergy among lymphoid cells mediating the graft-versus-host response. II. Synergy in graft-versus-host reactions produced by Balb-c lymphoid cells of differing anatomic origin. J Exp Med. 1970 Feb;131(2):235–246. doi: 10.1084/jem.131.2.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Cantor H., Simpson E. Regulation of the immune response by subclasses of T lymphocytes. I. Interactions between pre-killer T cells and regulatory T cells obtained from peripheral lymphoid tissues of mice. Eur J Immunol. 1975 May;5(5):330–336. doi: 10.1002/eji.1830050508. [DOI] [PubMed] [Google Scholar]
  9. Cohen G. H., Hopper J. A., Goldstein A. L. Thymosin-induced differentiation of murine thymocytes in allogeneic mixed lymphocyte cultures. Ann N Y Acad Sci. 1975 Feb 28;249:145–153. doi: 10.1111/j.1749-6632.1975.tb29064.x. [DOI] [PubMed] [Google Scholar]
  10. Cohen L., Howe M. L. Synergism between subpopulations of thymus-derived cells mediating the proliferative and effector phases of the mixed lymphocyte reaction. Proc Natl Acad Sci U S A. 1973 Sep;70(9):2707–2710. doi: 10.1073/pnas.70.9.2707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dardenne M., Bach J. F. Studies on thymus products. I. Modification of rosette-forming cells by thymic extracts. Determination of the target RFC sub-population. Immunology. 1973 Sep;25(3):343–352. [PMC free article] [PubMed] [Google Scholar]
  12. Dardenne M., Papiernik M., Bach J. F., Stutman O. Studies on thymus products. 3. Epithelial origin of the serum thymic factor. Immunology. 1974 Aug;27(2):299–304. [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Goldstein A. L., Low T. L., McAdoo M., McClure J., Thurman G. B., Rossio J., Lai C. Y., Chang D., Wang S. S., Harvey C. Thymosin alpha1: isolation and sequence analysis of an immunologically active thymic polypeptide. Proc Natl Acad Sci U S A. 1977 Feb;74(2):725–729. doi: 10.1073/pnas.74.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Goldstein A. L., Slater F. D., White A. Preparation, assay, and partial purification of a thymic lymphocytopoietic factor (thymosin). Proc Natl Acad Sci U S A. 1966 Sep;56(3):1010–1017. doi: 10.1073/pnas.56.3.1010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Goldstein G. Isolation of bovine thymin: a polypeptide hormone of the thymus. Nature. 1974 Jan 4;247(5435):11–14. doi: 10.1038/247011a0. [DOI] [PubMed] [Google Scholar]
  17. Goldstein G. The isolation of thymopoietin (thymin). Ann N Y Acad Sci. 1975 Feb 28;249:177–185. doi: 10.1111/j.1749-6632.1975.tb29067.x. [DOI] [PubMed] [Google Scholar]
  18. Hartzman R. J., Segall M., Bach M. L., Bach F. H. Histocompatibility matching. VI. Miniaturization of the mixed leukocyte culture test: a preliminary report. Transplantation. 1971 Mar;11(3):268–273. doi: 10.1097/00007890-197103000-00005. [DOI] [PubMed] [Google Scholar]
  19. Hodes R. J., Handwerger B. S., Terry W. D. Synergy between subpopulations of mouse spleen cells in the in vitro generation of cell-mediated cytotoxicity: evidence for the involvement of a non-T cell. J Exp Med. 1974 Dec 1;140(6):1646–1659. doi: 10.1084/jem.140.6.1646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Howard J. C., Scott D. W. The identification of sera distinguishing marrow-derived and thymus-derived lymphocytes in the rat thoracic duct. Immunology. 1974 Nov;27(5):903–922. [PMC free article] [PubMed] [Google Scholar]
  21. Howe M. L., Cohen L. Lymphoid cell subpopulations. I. Synergy between lymph node cells and thymocytes in response to alloantigens and mitogens. J Immunol. 1975 Nov;115(5):1227–1232. [PubMed] [Google Scholar]
  22. Häyry P., Andersson L. C. T cells in mixed-lymphocyte-culture-induced cytolysis (MLC-CML). Transplant Proc. 1973 Dec;5(4):1697–1703. [PubMed] [Google Scholar]
  23. Jacobsson H., Blomgren H. Enhancement of the mixed lymphocyte response in the mouse by addition of thymocytes. Cell Immunol. 1974 Feb;10(2):294–309. doi: 10.1016/0008-8749(74)90121-x. [DOI] [PubMed] [Google Scholar]
  24. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  25. Kook A. I., Trainin N. Hormone-like activity of a thymus humoral factor on the induction of immune competence in lymphoid cells. J Exp Med. 1974 Jan 1;139(1):193–207. doi: 10.1084/jem.139.1.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kook A. I., Trinin N. The control exerted by thymic hormone (THF) on cellular cAMP levels and immune reactivity of spleen cells in the MLC assay. J Immunol. 1975 Jul;115(1):8–14. [PubMed] [Google Scholar]
  27. Meredith P., Tittor W., DeLima M. G., Walford R. L. Age-related changes in the cellular immune response of lymph node and thymus cells in long-lived mice. Cell Immunol. 1975 Aug;18(2):324–330. doi: 10.1016/0008-8749(75)90060-x. [DOI] [PubMed] [Google Scholar]
  28. Peck A. B., Bach F. H. A miniaturized mouse mixed leukocyte culture in serum-free and mouse serum supplemented media. J Immunol Methods. 1973 Oct;3(2):147–163. doi: 10.1016/0022-1759(73)90030-6. [DOI] [PubMed] [Google Scholar]
  29. Plate J. M. Soluble factors substitute for T-T-cell collaboration in generation of T-killer lymphocytes. Nature. 1976 Mar 25;260(5549):329–331. doi: 10.1038/260329a0. [DOI] [PubMed] [Google Scholar]
  30. Plate J. M. Synergistic interactions between lymph node and thymus cells in response to antigenic differences limited to selected regions of the H-2 complex. Cell Immunol. 1976 Jan;21(1):121–132. doi: 10.1016/0008-8749(76)90333-6. [DOI] [PubMed] [Google Scholar]
  31. Rotter V., Globerson A., Nakamura I., Trainin N. Studies on characterization of the lymphoid target cell for activity of a thymus humoral factor. J Exp Med. 1973 Jul 1;138(1):130–142. doi: 10.1084/jem.138.1.130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sato V. L., Waksal S. D., Herzenberg L. A. Identification and separation of pre T-cells from nu/nu mice: differentiation by preculture with thymic reticuloepithelial cells. Cell Immunol. 1976 Jun 1;24(1):173–185. doi: 10.1016/0008-8749(76)90142-8. [DOI] [PubMed] [Google Scholar]
  33. Schendel D. J., Alter B. J., Bach F. H. The involvement of LD- and SD-region differences in MLC and CML: a three-cell experiment. Transplant Proc. 1973 Dec;5(4):1651–1655. [PubMed] [Google Scholar]
  34. Schlesinger D. H., Goldstein G. The amino acid sequence of thymopoietin II. Cell. 1975 Aug;5(4):361–365. doi: 10.1016/0092-8674(75)90054-9. [DOI] [PubMed] [Google Scholar]
  35. Tigelaar R. E., Asofsky R. Synergy among lymphoid cells mediating the graft-versus-host response. V. Derivation by migration in lethally irradiated recipients of two interacting subpopulations of thymus-derived cells from normal spleen. J Exp Med. 1973 Feb 1;137(2):239–253. doi: 10.1084/jem.137.2.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tigelaar R. E., Feldmann M. Synergy among thymocytes and peripheral lymph node cells in the in vitro generation of lymphocytes cytotoxic to alloantigens. Transplant Proc. 1973 Dec;5(4):1711–1715. [PubMed] [Google Scholar]
  37. Tigelaar R. E., Gorczynski R. M. Separable populations of activated thymus-derived lymphocytes identified in two assays for cell-mediated immunity to murine tumor allografts. J Exp Med. 1974 Jul 1;140(1):267–289. doi: 10.1084/jem.140.1.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Tittor W., Gerbase-Delima M., Walford R. L. Synergy among responding lymphoid cells in the one-way mixed lymphocyte reaction. Interaction between two types of thymus-dependent cells. J Exp Med. 1974 Jun 1;139(6):1488–1498. doi: 10.1084/jem.139.6.1488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Tittor W., Walford R. L. Synergistic response between thymus and lymph node cells in the mixed lymphocyte culture. Nature. 1974 Feb 8;247(5440):371–373. doi: 10.1038/247371a0. [DOI] [PubMed] [Google Scholar]
  40. Trainin N., Kook A. I., Umiel T., Albala M. The nature and mechanism of stimulation of immune responsiveness by thymus extracts. Ann N Y Acad Sci. 1975 Feb 28;249:349–361. doi: 10.1111/j.1749-6632.1975.tb29083.x. [DOI] [PubMed] [Google Scholar]
  41. Trainin N., Small M., Globerson A. Immunocompetence of spleen cells from neonatally thymectomized mice conferred in vitro by a syngeneic thymus extract. J Exp Med. 1969 Oct 1;130(4):765–775. doi: 10.1084/jem.130.4.765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Trainin N., Small M. Studies on some physicochemical properties of a thymus humoral factor conferring immunocompetence on lymphoid cells. J Exp Med. 1970 Nov;132(5):885–897. doi: 10.1084/jem.132.5.885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Umiel T., Trainin N. Increased reactivity of responding cells in the mixed lymphocyte reaction by a thymic humoral factor. Eur J Immunol. 1975 Feb;5(2):85–88. doi: 10.1002/eji.1830050203. [DOI] [PubMed] [Google Scholar]
  44. Wagner H. Cell-mediated immune responses in vitro: interaction of thymus-derived cells during cytotoxic allograft responses in vitro. Science. 1973 Sep 21;181(4105):1170–1172. doi: 10.1126/science.181.4105.1170. [DOI] [PubMed] [Google Scholar]
  45. Wagner H. Synergy during in vitro cytotoxic allograft responses. I. Evidence for cell interaction between thymocytes and peripheral T cells. J Exp Med. 1973 Dec 1;138(6):1379–1397. doi: 10.1084/jem.138.6.1379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Waksal S. D., Cohen I. R., Waksal H. W., Wekerle H., St Pierre R. L., Feldman M. Induction of T-cells differentiation in vitro by thymus epithelial cells. Ann N Y Acad Sci. 1975 Feb 28;249:492–498. doi: 10.1111/j.1749-6632.1975.tb29098.x. [DOI] [PubMed] [Google Scholar]

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