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. 1979 Jul;76(7):3507–3510. doi: 10.1073/pnas.76.7.3507

Help and suppression by lymphoid cells as a function of cellular concentration.

J Farrant, S C Knight
PMCID: PMC383856  PMID: 158761

Abstract

The phytohemagglutinin-stimulated uptake of [3H]thymidine in mixtures of human lymphocytes from the same source was shown to depend on the cell concentration in vitro as well as on the period of cultivation. "Helper" and "suppressor" effects were obtained by varying the concentration of cells and the periods of cultivation. The possibility that helper and suppressor subpopulations were responsible was avoided by mixing lymphoid cell line cells with others of the same monoclonal origin. Even under these conditions, both the direction and the extent of activity depended on the same two variables. This weakens the case for postulating the existence of distinct subpopulations of lymphocytes with helper or suppressor properties. This case was based on the use of damaging treatments believed to separate cell populations which were then found to differ in their helper and suppressor properties. We propose instead that the effect of such treatments is mediated through changes in the concentrations of interacting cells. Our data make it clear that the function of lymphoid cells ascertained in one set of conditions need not apply within a different cellular environment.

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Selected References

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

  1. Andersson J., Coutinho A., Melchers F. Stimulation of murine B lymphocytes to IgG synthesis and secretion by the mitogens lipopolysaccharide and lipoprotein and its inhibition by anti-immunoglobulin antibodies. Eur J Immunol. 1978 May;8(5):336–343. doi: 10.1002/eji.1830080509. [DOI] [PubMed] [Google Scholar]
  2. Andersson J., Coutinho A., Melchers F., Watanabe T. Growth and maturation of single clones of normal murine T and B lymphocytes in vitro. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):227–236. doi: 10.1101/sqb.1977.041.01.028. [DOI] [PubMed] [Google Scholar]
  3. Beverley P. C., Woody J., Dunkley M., Feldmann M., McKenzie I. Separation of suppressor and killer T cells by surgace phenotype. Nature. 1976 Aug 5;262(5568):495–497. doi: 10.1038/262495a0. [DOI] [PubMed] [Google Scholar]
  4. Brent L., Medawar P. Quantitative studies on tissue transplantation immunity. VII. The normal lymphocyte transfer reaction. Proc R Soc Lond B Biol Sci. 1966 Sep 13;165(1000):281–307. doi: 10.1098/rspb.1966.0069. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Cantor H., Boyse E. A. Regulation of cellular and humoral immune responses by T-cell subclasses. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):23–32. doi: 10.1101/sqb.1977.041.01.006. [DOI] [PubMed] [Google Scholar]
  8. Corley R. B., Kindred B. In vivo responses of alloreactive lymphocytes stimulated in vitro. Helper-cell activity of MLR-primed lymphocytes. Scand J Immunol. 1977;6(9):923–932. doi: 10.1111/j.1365-3083.1977.tb00413.x. [DOI] [PubMed] [Google Scholar]
  9. Corley R. B., Kindred B. In vivo responses of alloreactive lymphocytes stimulated in vitro. Skin graft rejection mediated by MLR-Primed lymphocytes. Scand J Immunol. 1977;6(10):991–996. doi: 10.1111/j.1365-3083.1977.tb00334.x. [DOI] [PubMed] [Google Scholar]
  10. Corley R. B., Kindred B., Lefkovits I. Positive and negative allogeneic effects mediated by MLR-primed lymphocytes: quantitation by limiting dilution analysis. J Immunol. 1978 Sep;121(3):1082–1089. [PubMed] [Google Scholar]
  11. Corley R. B. Responses of alloantigen-primed lymphocytes in vitro. The contribution of increased frequencies of responding lymphocytes to differences between reactivity of normal and primed lymphocyte populations. Scand J Immunol. 1977;6(6-7):625–633. doi: 10.1111/j.1365-3083.1977.tb02142.x. [DOI] [PubMed] [Google Scholar]
  12. Coutinho A., Möller G. Thymus-independent B-cell induction and paralysis. Adv Immunol. 1975;21:113–236. doi: 10.1016/s0065-2776(08)60220-5. [DOI] [PubMed] [Google Scholar]
  13. Darzynkiewicz Z., Balazs E. A. Effect of connective tissue intercellular matrix on lymphocyte stimulation. Exp Cell Res. 1971 May;66(1):113–123. doi: 10.1016/s0014-4827(71)80018-6. [DOI] [PubMed] [Google Scholar]
  14. Eardley D. D., Staskawicz M. O., Gershon R. K. Suppressor cells: dependence on assay conditions for functional activity. J Exp Med. 1976 May 1;143(5):1211–1219. doi: 10.1084/jem.143.5.1211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fitch F. W., Engers H. D., MacDonald H. R., Cerottini J. C., Brunner K. T. Generation of cytotoxic T lymphocytes in vitro. VI. Effect of cell density on response in mixed leukocyte cultures. J Immunol. 1975 Dec;115(6):1688–1694. [PubMed] [Google Scholar]
  16. Herzenberg L. A., Okumura K., Cantor H., Sato V. L., Shen F. W., Boyse E. A., Herzenberg L. A. T-cell regulation of antibody responses: demonstration of allotype-specific helper T cells and their specific removal by suppressor T cells. J Exp Med. 1976 Aug 1;144(2):330–344. doi: 10.1084/jem.144.2.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hunninghake G. W., Fauci A. S. Suppression of the generation of human con A-induced cytotoxic effector cells by con A-activated suppressor cells. J Immunol. 1978 Jun;120(6):1828–1831. [PubMed] [Google Scholar]
  18. Jandinski J., Cantor H., Tadakuma T., Peavy D. L., Pierce C. W. Separation of helper T cells from suppressor T cells expressing different Ly components. I. Polyclonal activation: suppressor and helper activities are inherent properties of distinct T-cell subclasses. J Exp Med. 1976 Jun 1;143(6):1382–1390. doi: 10.1084/jem.143.6.1382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kettman J., Dutton R. W. Radioresistance of the enhancing effect of cells from carrier-immunized mice in an in vitro primary immune response. Proc Natl Acad Sci U S A. 1971 Apr;68(4):699–703. doi: 10.1073/pnas.68.4.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Knight S. C., Farrant J. Comparing stimulation of lymphocytes in different samples: separate effects of numbers of responding cells and their capacity to respond. J Immunol Methods. 1978;22(1-2):63–71. doi: 10.1016/0022-1759(78)90058-3. [DOI] [PubMed] [Google Scholar]
  21. Kyminski J. W., Smith R. T. Evidence for a B-cell -like helper function in mixed lymphocyte culture between immunocompetent thymus cells. J Exp Med. 1975 Feb 1;141(2):360–373. doi: 10.1084/jem.141.2.360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kyminski J. W., Smith R. T. Evidence for a B-cell -like helper function in mixed lymphocyte culture between immunocompetent thymus cells. J Exp Med. 1975 Feb 1;141(2):360–373. doi: 10.1084/jem.141.2.360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. MacDonald H. R. Restimulation of cytolytic T-lymphocytes in long-term mixed leukocyte cultures. 1. Physical and proliferative characteristics of cytolytic T-lymphocytes restimulated at low cell density. Cell Immunol. 1978 Feb;35(2):414–426. doi: 10.1016/0008-8749(78)90160-0. [DOI] [PubMed] [Google Scholar]
  24. McMichael A. J., Sasazuki T. A suppressor T cell in the human mixed lymphocyte reaction. J Exp Med. 1977 Aug 1;146(2):368–380. doi: 10.1084/jem.146.2.368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Melchers F., Coutinho A., Heinrich G., Andersson J. Continuous growth of mitogen-reactive B lymphocytes. Scand J Immunol. 1975;4(8):853–858. doi: 10.1111/j.1365-3083.1975.tb03728.x. [DOI] [PubMed] [Google Scholar]
  26. Milton J. D., Carpenter C. B., Addison I. E. Depressed T-cell reactivity and suppressor activity of lymoid cells from cyclophosphamide-treated mice. Cell Immunol. 1976 Jun 15;24(2):308–317. doi: 10.1016/0008-8749(76)90214-8. [DOI] [PubMed] [Google Scholar]
  27. Moretta L., Webb S. R., Grossi C. E., Lydyard P. M., Cooper M. D. Functional analysis of two human T-cell subpopulations: help and suppression of B-cell responses by T cells bearing receptors for IgM or IgG. J Exp Med. 1977 Jul 1;146(1):184–200. doi: 10.1084/jem.146.1.184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rich S. S., Rich R. R. Regulatory mechanisms in cell-mediated immune responses. I. Regulation of mixed lymphocyte reactions by alloantigen-activated thymus-derived lymphocytes. J Exp Med. 1974 Dec 1;140(6):1588–1603. doi: 10.1084/jem.140.6.1588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rook G. A., King J. Is the adherent, non-specific 'suppressor' cell from rodent spleens an in vitro artefact? Clin Exp Immunol. 1978 Jun;32(3):466–470. [PMC free article] [PubMed] [Google Scholar]
  30. Scavulli J., Dutton R. W. Competition between concanavalin A-induced stimulatory and inhibitory effects in the in vitro immune response to antigen. J Exp Med. 1975 Feb 1;141(2):524–529. doi: 10.1084/jem.141.2.524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Schellekens P. T., Eijsvoogel V. P. Lymphocyte transformation in vitro. I. Tissue culture conditions and quantitative measurements. Clin Exp Immunol. 1968 Jul;3(6):571–584. [PMC free article] [PubMed] [Google Scholar]
  32. Sims T., Clagett J. A., Page R. C. Effects of cell concentration and exogenous prostaglandin on the interaction and responsiveness of human peripheral blood leukocytes. Clin Immunol Immunopathol. 1979 Feb;12(2):150–161. doi: 10.1016/0090-1229(79)90004-7. [DOI] [PubMed] [Google Scholar]
  33. Swain S. L., Dutton R. W. Negative allogeneic effects in vitro. I. Allogeneic T cells markedly suppress the secondary antibody-forming cell response. J Immunol. 1977 Jun;118(6):2262–2268. [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. Tse H. Y., Dutton R. W. Separation of helper and suppressor T lymphocytes. III. Positive and negative effects of mixed lymphocyte reaction-activated T cells. J Immunol. 1978 Apr;120(4):1149–1152. [PubMed] [Google Scholar]
  37. Tse H., Dutton R. W. Separation of helper and suppressor T lymphocytes on a ficoll velocity sedimentation gradient. J Exp Med. 1976 May 1;143(5):1199–1210. doi: 10.1084/jem.143.5.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Winger L. A., Nowell P. C., Daniele R. P. Sequential proliferation induced in human peripheral blood lymphocytes by mitogen. I. Growth of 1000 lymphocytes in feeder layer cultures. J Immunol. 1977 May;118(5):1763–1767. [PubMed] [Google Scholar]
  39. Winger L. A., Nowell P. C., Daniele R. P. Sequential proliferation induced in human peripheral blood lymphocytes by mitogen. II. Suppression by PHA-activated cells. J Immunol. 1977 May;118(5):1768–1773. [PubMed] [Google Scholar]

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