Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1981 Sep;44(1):75–87.

The rat mixed lymphocyte reaction: roles of a dendritic cell in intestinal lymph and T-cell subsets defined by monoclonal antibodies.

D W Mason, C W Pugh, M Webb
PMCID: PMC1555124  PMID: 6456222

Abstract

Cells present in the intestinal lymph of rats were obtained in large numbers by removing the mesenteric, portal and caecal lymph nodes and cannulating the thoracic duct 6 weeks later. About 1% of the cells present in the thoracic duct lymph of these mesenteric lymphadenectomized rats had striking dendritic morphology, were strongly Ia+ but labelled weakly with monoclonal antibodies that recognize rat B or T cells. It was found that intestinal lymph was highly enriched for cells that stimulated allogeneic T cells in the mixed lymphocyte reaction (MLR) and cells with stimulator activity co-purified with dendritic cells. Thus, these dendritic cells appear phenotypically and functionally similar to the dendritic cells that have been described in the mouse spleen and rat lymph node. The ability of the intestinal lymph cells to stimulate rat T cells was used to determine which of the two subsets of these cells were the prime responders in the rat MLR. These subsets, defined by monoclonal antibodies, have been shown by previous work to display close functional analogies to the Lyt 2+ and Lyt 2- subsets in the mouse and to the two human T-cell subsets that have been defined by monoclonal antibodies. It was found that the T-cell subset that contains the helper cells for antibody responses proliferated when irradiated, fully allogeneic or semi-allogeneic thoracic duct cells were used as stimulators, but the subset containing suppressor T cells did so only in the fully allogeneic system. Detailed studies showed that in the absence of helper cells in the responder population T cells in the stimulator population of helper phenotype were responsible for proliferation of the suppressor T-cell subset observed in fully allogeneic MLRs. Proliferation of the suppressor T-cell subset could be obtained using semi-allogeneic stimulators, provided that the F1 cells were derived from a source containing dendritic cells but it was shown that, as in the case with fully allogeneic stimulators, the helper T cells in the stimulator population were playing an active role. These results demonstrate that proliferation of the suppressor T-cell subset in the rat MLR is dependent on blastogenic activity provided by the helper T-cell subset and suggest that in some situations this blastogenic activity may arise through the recognition, by the helper cells, of environmental antigens presented on dendritic cells. It has been reported that in the human MLR both T-cell subsets proliferate but that only the helper subset does so when antigen-primed cells are stimulated with specific antigen. The present experiments, by emphasizing the activity of helper T cells in the stimulator population in the MLR, cast doubt on the implication that recognition of alloantigens in vitro differs in an essential way from that of soluble antigens.

Full text

PDF
76

Selected References

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

  1. Antczak D. F., Brown D., Howard J. C. Analysis of lymphocytes reactive to histocompatibility antigens. I. A quantitative titration assay for mixed lymphocyte interactions in the rat. Cell Immunol. 1979 Mar 15;43(2):304–316. doi: 10.1016/0008-8749(79)90175-8. [DOI] [PubMed] [Google Scholar]
  2. Barclay A. N. The localization of populations of lymphocytes defined by monoclonal antibodies in rat lymphoid tissues. Immunology. 1981 Apr;42(4):593–600. [PMC free article] [PubMed] [Google Scholar]
  3. Bell E. B. Antigen-laden cells in thoracic duct lymph. Implications for adoptive transfer experiments. Immunology. 1979 Dec;38(4):797–808. [PMC free article] [PubMed] [Google Scholar]
  4. Brideau R. J., Carter P. B., McMaster W. R., Mason D. W., Williams A. F. Two subsets of rat T lymphocytes defined with monoclonal antibodies. Eur J Immunol. 1980 Aug;10(8):609–615. doi: 10.1002/eji.1830100807. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. England J. M., Rogers A. W., Miller R. G., Jr The identification of labelled structures on autoradiographs. Nature. 1973 Apr 27;242(5400):612–613. doi: 10.1038/242612a0. [DOI] [PubMed] [Google Scholar]
  7. Galfrè G., Milstein C., Wright B. Rat x rat hybrid myelomas and a monoclonal anti-Fd portion of mouse IgG. Nature. 1979 Jan 11;277(5692):131–133. doi: 10.1038/277131a0. [DOI] [PubMed] [Google Scholar]
  8. Goud T. J., Schotte C., van Furth R. Identification and characterization of the monoblast in mononuclear phagocyte colonies grown in vitro. J Exp Med. 1975 Nov 1;142(5):1180–1199. doi: 10.1084/jem.142.5.1180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jensenius J. C., Williams A. F. The binding of anti-immunoglobulin antibodies to rat thymocytes and thoracic duct lymphocytes. Eur J Immunol. 1974 Feb;4(2):91–97. doi: 10.1002/eji.1830040207. [DOI] [PubMed] [Google Scholar]
  10. Klinkert W. E., LaBadie J. H., O'Brien J. P., Beyer C. F., Bowers W. E. Rat dendritic cells function as accessory cells and control the production of a soluble factor required for mitogenic responses of T lymphocytes. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5414–5418. doi: 10.1073/pnas.77.9.5414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Loken M. R., Herzenber L. A. Analysis of cell populations with a fluorescence-activated cell sorter. Ann N Y Acad Sci. 1975 Jun 30;254:163–171. doi: 10.1111/j.1749-6632.1975.tb29166.x. [DOI] [PubMed] [Google Scholar]
  12. Loop S. M., Bernstein I. D., Wright P. W. T cell synergy in the rat: serologic characterization of T cell subsets. J Immunol. 1980 Sep;125(3):1237–1239. [PubMed] [Google Scholar]
  13. MANN J. D., HIGGINS G. M. Lymphocytes in thoracic duct intestinal and hepatic lymph. Blood. 1950 Feb;5(2):177–190. [PubMed] [Google Scholar]
  14. Mason D. W., Gallico G. G. Tissue distribution and quantitation of Ia-like antigens in the rat. Eur J Immunol. 1978 Oct;8(10):741–748. doi: 10.1002/eji.1830081013. [DOI] [PubMed] [Google Scholar]
  15. McMaster W. R., Williams A. F. Identification of Ia glycoproteins in rat thymus and purification from rat spleen. Eur J Immunol. 1979 Jun;9(6):426–433. doi: 10.1002/eji.1830090603. [DOI] [PubMed] [Google Scholar]
  16. Nussenzweig M. C., Steinman R. M. Contribution of dendritic cells to stimulation of the murine syngeneic mixed leukocyte reaction. J Exp Med. 1980 May 1;151(5):1196–1212. doi: 10.1084/jem.151.5.1196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Reinherz E. L., Kung P. C., Breard J. M., Goldstein G., Schlossman S. F. T cell requirements for generation of helper factor(s) in man: analysis of the subsets involved. J Immunol. 1980 Apr;124(4):1883–1887. [PubMed] [Google Scholar]
  18. Reinherz E. L., Schlossman S. F. The differentiation and function of human T lymphocytes. Cell. 1980 Apr;19(4):821–827. doi: 10.1016/0092-8674(80)90072-0. [DOI] [PubMed] [Google Scholar]
  19. Rolstad B., Williams A. F., Ford W. L. The alloantibody response to a strong transplantation antigen (Ag-B). Quantitative aspects and thymus dependence of the response. Transplantation. 1974 Apr;17(4):416–423. doi: 10.1097/00007890-197404000-00013. [DOI] [PubMed] [Google Scholar]
  20. Roser B. J. The origin and significance of macrophages in thoracic duct lymph. Aust J Exp Biol Med Sci. 1976 Dec;54(6):541–550. doi: 10.1038/icb.1976.55. [DOI] [PubMed] [Google Scholar]
  21. Schrier R. D., Skidmore B. J., Kurnick J. T., Goldstine S. N., Chiller J. M. Propagation of antigen-specific T cell helper function in vitro. J Immunol. 1979 Dec;123(6):2525–2531. [PubMed] [Google Scholar]
  22. Smith K. A. T-cell growth factor. Immunol Rev. 1980;51:337–357. doi: 10.1111/j.1600-065x.1980.tb00327.x. [DOI] [PubMed] [Google Scholar]
  23. Steinman R. M., Cohn Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med. 1973 May 1;137(5):1142–1162. doi: 10.1084/jem.137.5.1142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Steinman R. M., Witmer M. D. Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5132–5136. doi: 10.1073/pnas.75.10.5132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tilney N. L. Patterns of lymphatic drainage in the adult laboratory rat. J Anat. 1971 Sep;109(Pt 3):369–383. [PMC free article] [PubMed] [Google Scholar]
  26. Webb M., Mason D. W., Williams A. F. Inhibition of mixed lymphocyte response by monoclonal antibody specific for a rat T lymphocyte subset. Nature. 1979 Dec 20;282(5741):841–843. doi: 10.1038/282841a0. [DOI] [PubMed] [Google Scholar]
  27. White R. A., Mason D. W., Williams A. F., Galfre G., Milstein C. T-lymphocyte heterogeneity in the rat: separation of functional subpopulations using a monoclonal antibody. J Exp Med. 1978 Sep 1;148(3):664–673. doi: 10.1084/jem.148.3.664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Williams A. F., Galfrè G., Milstein C. Analysis of cell surfaces by xenogeneic myeloma-hybrid antibodies: differentiation antigens of rat lymphocytes. Cell. 1977 Nov;12(3):663–673. doi: 10.1016/0092-8674(77)90266-5. [DOI] [PubMed] [Google Scholar]
  29. von Boechmer H. Separation of T and B lymphocytes and their role in the mixed lymphocyte reaction. J Immunol. 1974 Jan;112(1):70–78. [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES