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. 1974 Nov 30;140(6):1588–1603. doi: 10.1084/jem.140.6.1588

REGULATORY MECHANISMS IN CELL-MEDIATED IMMUNE RESPONSES

I. Regulation of Mixed Lymphocyte Reactions by Alloantigen-Activated Thymus-Derived Lymphocytes

Susan Solliday Rich 1, Robert R Rich 1
PMCID: PMC2139756  PMID: 4279271

Abstract

Regulatory effects of alloantigen-activated thymus-derived lymphocytes in mixed lymphocyte reactions have been demonstrated. Mice were injected into foot pads with allogeneic spleen cells; 4 days following sensitization spleen or regional lymph node cells from these animals were treated with mitomycin C and incorporated into MLR as regulator populations syngeneic to the responder cell type. Activated spleen cells suppressed MLR responses 60–90% whereas activated lymph node cells from the same animals enhanced MLR responses. Suppression by activated spleen cells was not due to cytotoxic effects nor to altered kinetics of the proliferative response. Studies of splenic suppressor cell generation in vivo revealed peak activity four days after alloantigen stimulation with no activity demonstrable at 7 days or at later times. Suppressor cell activity was abrogated by treatment with anti-θC3H serum and complement, and was not alloantigen specific.

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Selected References

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  1. Adler W. H., Takiguchi T., Marsh B., Smith R. T. Cellular recognition by mouse lymphocytes in vitro. II. Specific stimulation by histocompatibility antigens in mixed cell culture. J Immunol. 1970 Oct;105(4):984–1000. [PubMed] [Google Scholar]
  2. Bach F. H., Segall M., Zier K. S., Sondel P. M., Alter B. J., Bach M. L. Cell mediated immunity: separation of cells involved in recognitive and destructive phases. Science. 1973 Apr 27;180(4084):403–406. doi: 10.1126/science.180.4084.403. [DOI] [PubMed] [Google Scholar]
  3. Bach M. L., Alter B. J., Lightbody J. J., Bach F. H. Abrogation of cytotoxicity of mixed leukocyte cultures. Transplant Proc. 1972 Jun;4(2):169–172. [PubMed] [Google Scholar]
  4. Badger A. M., Cooperband S. R., Green J. A. Culture conditions affecting induction and release of lymphocyte produced proliferation inhibitory factor (PIF). Cell Immunol. 1973 Jul;8(1):12–27. doi: 10.1016/0008-8749(73)90089-0. [DOI] [PubMed] [Google Scholar]
  5. Barchilon J., Liebhaber S. A., Gershon R. K. Significance of cell interactions in production of graft versus host splenomegaly. Yale J Biol Med. 1972 Oct;45(5):519–529. [PMC free article] [PubMed] [Google Scholar]
  6. Brunner K. T., Mauel J., Cerottini J. C., Chapuis B. Quantitative assay of the lytic action of immune lymphoid cells on 51-Cr-labelled allogeneic target cells in vitro; inhibition by isoantibody and by drugs. Immunology. 1968 Feb;14(2):181–196. [PMC free article] [PubMed] [Google Scholar]
  7. Brunner K. T., Mauel J., Rudolf H., Chapuis B. Studies of allograft immunity in mice. I. Induction, development and in vitro assay of cellular immunity. Immunology. 1970 Apr;18(4):501–515. [PMC free article] [PubMed] [Google Scholar]
  8. Cantor H., Asofsky R. Synergy among lymphoid cells mediating the graft-versus-host response. 3. Evidence for interaction between two types of thymus-derived cells. J Exp Med. 1972 Apr 1;135(4):764–779. doi: 10.1084/jem.135.4.764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Cantor H., Asofsky R., Talal N. Synergy among lymphoid cells mediating the graft-versus-host response. I. Synergy in graft-versus-host reactions produced by cells from NZB-Bl mice. J Exp Med. 1970 Feb;131(2):223–234. doi: 10.1084/jem.131.2.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Claman H. N., Chaperon E. A. Immunologic complementation between thymus and marrow cells--a model for the two-cell theory of immunocompetence. Transplant Rev. 1969;1:92–113. doi: 10.1111/j.1600-065x.1969.tb00137.x. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Diamond B., Knight S. C., Lance E. M. Some observations on the in vitro reactivity of lymphoid subpopulations. Cell Immunol. 1974 Mar 30;11(1-3):239–246. doi: 10.1016/0008-8749(74)90024-0. [DOI] [PubMed] [Google Scholar]
  14. Dutton R. W. Inhibitory and stimulatory effects of concanavalin A on the response of mouse spleen cell suspensions to antigen. II. Evidence for separate stimulatory and inhibitory cells. J Exp Med. 1973 Dec 1;138(6):1496–1505. doi: 10.1084/jem.138.6.1496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Folch H., Waksman B. H. The splenic suppressor cell. I. Activity of thymus-dependent adherent cells: changes with age and stress. J Immunol. 1974 Jul;113(1):127–139. [PubMed] [Google Scholar]
  16. Folch H., Waksman B. H. The splenic suppressor cell. II. Suppression of mixed lymphocyte reaction by thymus-dependent adherent cells. J Immunol. 1974 Jul;113(1):140–144. [PubMed] [Google Scholar]
  17. Gershon R. K., Lance E. M., Kondo K. Immuno-regulatory role of spleen localizing thymocytes. J Immunol. 1974 Feb;112(2):546–554. [PubMed] [Google Scholar]
  18. Gershon R. K., Liebhaber S., Ryu S. T-cell regulation of T-cell responses to antigen. Immunology. 1974 May;26(5):909–923. [PMC free article] [PubMed] [Google Scholar]
  19. Green J. A., Cooperband S. R., Rutstein J. A., Kibrick S. Inhibition of target cell proliferation by supernatants from cultures of human peripheral lymphocytes. J Immunol. 1970 Jul;105(1):48–54. [PubMed] [Google Scholar]
  20. Hardin J. A., Chused T. M., Steinberg A. D. Supressor cells in the graft vs host reaction. J Immunol. 1973 Aug;111(2):650–651. [PubMed] [Google Scholar]
  21. Holzman R. S., Lebowitz A. S., Valentine F. T., Lawrence H. S. Preparation and properties of cloning inhibitory factor. I. Inhibition of HeLa cell cloning by stimulated lymphocytes and their culture supernatants. Cell Immunol. 1973 Aug;8(2):249–258. doi: 10.1016/0008-8749(73)90114-7. [DOI] [PubMed] [Google Scholar]
  22. Häyry P., Andersson L. C., Nordling S., Virolainen M. Allograft response in vitro. Transplant Rev. 1972;12:91–140. doi: 10.1111/j.1600-065x.1972.tb00054.x. [DOI] [PubMed] [Google Scholar]
  23. Katz D. H., Benacerraf B. The regulatory influence of activated T cells on B cell responses to antigen. Adv Immunol. 1972;15:1–94. doi: 10.1016/s0065-2776(08)60683-5. [DOI] [PubMed] [Google Scholar]
  24. Lance E., Cooper S. Functional properties of segregated lymphocytes. Transplant Proc. 1973 Mar;5(1):119–124. [PubMed] [Google Scholar]
  25. MITCHISON N. A. Studies on the immunological response to foreign tumor transplants in the mouse. I. The role of lymph node cells in conferring immunity by adoptive transfer. J Exp Med. 1955 Aug 1;102(2):157–177. doi: 10.1084/jem.102.2.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Miller J. F., Mitchell G. F. Thymus and antigen-reactive cells. Transplant Rev. 1969;1:3–42. doi: 10.1111/j.1600-065x.1969.tb00135.x. [DOI] [PubMed] [Google Scholar]
  27. Peavy D. L., Pierce C. W. Cell-mediated immune responses in vitro. I. Suppression of the generation of cytotoxic lymphocytes by concanavalin A and concanavalin A-activated spleen cells. J Exp Med. 1974 Aug 1;140(2):356–369. doi: 10.1084/jem.140.2.356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rich R. R., Pierce C. W. Biological expressions of lymphocyte activation. 3. Suppression of plaque-forming cell responses in vitro by supernatant fluids from concanavalin A-activated spleen cell cultures. J Immunol. 1974 Apr;112(4):1360–1368. [PubMed] [Google Scholar]
  29. Rich R. R., Pierce C. W. Biological expressions of lymphocyte activation. II. Generation of a population of thymus-derived suppressor lymphocytes. J Exp Med. 1973 Mar 1;137(3):649–659. doi: 10.1084/jem.137.3.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rocklin R. E. Production of migration inhibitory factor by non-dividing lymphocytes. J Immunol. 1973 Mar;110(3):674–678. [PubMed] [Google Scholar]
  31. Taussig M. J. Demonstration of suppressor T cells in a population of 'educated' T cells. Nature. 1974 Mar 15;248(445):236–238. doi: 10.1038/248236a0. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. Zembala M., Asherson G. L. Depression of the T cell phenomenon of contact sensitivity by T cells from unresponsive mice. Nature. 1973 Jul 27;244(5413):227–228. doi: 10.1038/244227a0. [DOI] [PubMed] [Google Scholar]

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