Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1989 Mar;75(3):432–437.

The role of human alveolar macrophages in the allogeneic and autologous mixed leucocyte reactions.

D B Ettensohn 1, P G Duncan 1, M J Jankowski 1
PMCID: PMC1541973  PMID: 2522843

Abstract

Human alveolar macrophages (AM) are deficient in their ability to promote antigen-stimulated lymphocyte proliferation when compared to in-vitro-aged blood derived macrophages (BM). The mechanisms behind the unique accessory cell function of human AM are unknown. The current paradigm for accessory cell function requires antigen presentation in the context of gene products of the HLA-DR locus of the major histocompatibility complex (Class II, DR antigens) and secretion of non-specific second signal (e.g. interleukin 1). While both AM and in-vitro-aged BM have limited ability to secrete interleukin 1 (IL-1), more than 90% of both cell types express DR antigens. However, only BM consistently promote antigen-stimulated lymphocyte proliferation. Addition of IL-1 does not restore accessory cell function of human AM for antigen stimulation. It is possible that DR antigen expression and/or function of AM may be more contributory for their accessory cell function. The mixed leucocyte reaction (MLR) and autologous mixed leucocyte reactions (AMLR) in which DR epitopes stimulate proliferation of allogeneic and autologous T cells, respectively, are useful in vitro assays for assessment of DR-restricted macrophage-lymphocyte interactions. In the current studies we demonstrate that AM are usually equivalent to autologous in-vitro-aged BM in their ability to stimulate an MLR, but are consistently deficient relative to such BM in their ability to stimulate an AMLR. Experiments in which the two cells were co-cultured indicate that AM-mediated suppression does not account for the limited ability of AM to stimulate an AMLR. The deficiency of AM to act as accessory cells for antigen-stimulated lymphocyte proliferation may relate to their relative inability to stimulate autoreactive T cells and be attributable to differences in DR antigen expression and/or function.

Full text

PDF
432

Selected References

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

  1. Coeshott C. M., Chesnut R. W., Kubo R. T., Grammer S. F., Jenis D. M., Grey H. M. Ia-specific mixed leukocyte reactive T cell hybridomas: analysis of their specificity by using purified class II MHC molecules in synthetic membrane system. J Immunol. 1986 Apr 15;136(8):2832–2838. [PubMed] [Google Scholar]
  2. Cowing C., Chapdelaine J. M. T cells discriminate between Ia antigens expressed on allogeneic accessory cells and B cells: a potential function for carbohydrate side chains on Ia molecules. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6000–6004. doi: 10.1073/pnas.80.19.6000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. DuPont B., Hansen J. A. Human mixed-lymphocyte culture reaction: genetics, specificity, and biological implications. Adv Immunol. 1976;23:107–202. doi: 10.1016/s0065-2776(08)60320-x. [DOI] [PubMed] [Google Scholar]
  4. Elias J. A., Schreiber A. D., Gustilo K., Chien P., Rossman M. D., Lammie P. J., Daniele R. P. Differential interleukin 1 elaboration by unfractionated and density fractionated human alveolar macrophages and blood monocytes: relationship to cell maturity. J Immunol. 1985 Nov;135(5):3198–3204. [PubMed] [Google Scholar]
  5. Esa A. H., Noga S. J., Donnenberg A. D., Hess A. D. Immunological heterogeneity of human monocyte subsets prepared by counterflow centrifugation elutriation. Immunology. 1986 Sep;59(1):95–99. [PMC free article] [PubMed] [Google Scholar]
  6. Ettensohn D. B., Jankowski M. J., Duncan P. G., Lalor P. A. Bronchoalveolar lavage in the normal volunteer subject. I. Technical aspects and intersubject variability. Chest. 1988 Aug;94(2):275–280. doi: 10.1378/chest.94.2.275. [DOI] [PubMed] [Google Scholar]
  7. Ettensohn D. B., Lalor P. A., Roberts N. J., Jr Human alveolar macrophage regulation of lymphocyte proliferation. Am Rev Respir Dis. 1986 Jun;133(6):1091–1096. doi: 10.1164/arrd.1986.133.6.1091. [DOI] [PubMed] [Google Scholar]
  8. Ettensohn D. B., Roberts N. J., Jr Human alveolar macrophage support of lymphocyte responses to mitogens and antigens. Analysis and comparison with autologous peripheral-blood-derived monocytes and macrophages. Am Rev Respir Dis. 1983 Sep;128(3):516–522. doi: 10.1164/arrd.1983.128.3.516. [DOI] [PubMed] [Google Scholar]
  9. Ferro T. J., Kern J. A., Elias J. A., Kamoun M., Daniele R. P., Rossman M. D. Alveolar macrophages, blood monocytes, and density-fractionated alveolar macrophages differ in their ability to promote lymphocyte proliferation to mitogen and antigen. Am Rev Respir Dis. 1987 Mar;135(3):682–687. doi: 10.1164/arrd.1987.135.3.682. [DOI] [PubMed] [Google Scholar]
  10. Ferro T. J., Monos D. S., Spear B. T., Rossman M. D., Zmijewski C. M., Kamoun M., Daniele R. P. Carbohydrate differences in HLA-DR molecules synthesized by alveolar macrophages and blood monocytes. Am Rev Respir Dis. 1987 Jun;135(6):1340–1344. doi: 10.1164/arrd.1987.135.6.1340. [DOI] [PubMed] [Google Scholar]
  11. Germain R. N. Accessory cell stimulation of T cell proliferation requires active antigen processing, Ia-restricted antigen presentation, and a separate nonspecific 2nd signal. J Immunol. 1981 Nov;127(5):1964–1966. [PubMed] [Google Scholar]
  12. Golding H., Singer A. Role of accessory cell processing and presentation of shed H-2 alloantigens in allospecific cytotoxic T lymphocyte responses. J Immunol. 1984 Aug;133(2):597–605. [PubMed] [Google Scholar]
  13. Haq A. U., Mayernik D. G., Orosz C., Rinehart J. J. Interleukin 1 secretion is not required for human macrophage support of T-cell proliferation. Cell Immunol. 1984 Sep;87(2):517–527. doi: 10.1016/0008-8749(84)90020-0. [DOI] [PubMed] [Google Scholar]
  14. Katz D. R., Feldmann M., Tees R., Schreier M. H. Heterogeneity of accessory cells interacting with T-helper clones. Immunology. 1986 Jun;58(2):167–172. [PMC free article] [PubMed] [Google Scholar]
  15. Kaufmann S. H., Simon M. M., Hahn H. Regulatory interactions between macrophages and T-cell subsets in Listeria monocytogenes-specific T-cell activation. Infect Immun. 1982 Dec;38(3):907–913. doi: 10.1128/iai.38.3.907-913.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kouzan S., Nolan R. D., Fournier T., Bignon J., Eling T. E., Brody A. R. Stimulation of arachidonic acid metabolism by adherence of alveolar macrophages to a plastic substrate. Modulation by fetal bovine serum. Am Rev Respir Dis. 1988 Jan;137(1):38–43. doi: 10.1164/ajrccm/137.1.38. [DOI] [PubMed] [Google Scholar]
  17. Lee S. H., Matsuyama T., Logalbo P., Silver J., Winchester R. J. Ia antigens and susceptibility to rheumatoid arthritis. Clin Rheum Dis. 1985 Dec;11(3):645–664. [PubMed] [Google Scholar]
  18. Lipscomb M. F., Lyons C. R., Nunez G., Ball E. J., Stastny P., Vial W., Lem V., Weissler J., Miller L. M. Human alveolar macrophages: HLA-DR-positive macrophages that are poor stimulators of a primary mixed leukocyte reaction. J Immunol. 1986 Jan;136(2):497–504. [PubMed] [Google Scholar]
  19. Lyons C. R., Ball E. J., Toews G. B., Weissler J. C., Stastny P., Lipscomb M. F. Inability of human alveolar macrophages to stimulate resting T cells correlates with decreased antigen-specific T cell-macrophage binding. J Immunol. 1986 Aug 15;137(4):1173–1180. [PubMed] [Google Scholar]
  20. Mayernik D. G., Ul-Haq A., Rinehart J. J. Differentiation-associated alteration in human monocyte-macrophage accessory cell function. J Immunol. 1983 May;130(5):2156–2160. [PubMed] [Google Scholar]
  21. Naito K., Komatsubara S., Kawai J., Mori K., Muramatsu S. Role of macrophages as modulators but not as stimulators in primary mixed leukocyte reaction. Cell Immunol. 1984 Oct 15;88(2):361–373. doi: 10.1016/0008-8749(84)90169-2. [DOI] [PubMed] [Google Scholar]
  22. Nakamura R. M., Tanaka H., Tokunaga T. In vitro induction of suppressor T-cells in delayed-type hypersensitivity to BCG and an essential role of I-J positive accessory cells. Immunol Lett. 1982 Jun;4(6):295–299. doi: 10.1016/0165-2478(82)90055-4. [DOI] [PubMed] [Google Scholar]
  23. Raff H. V., Picker L. J., Stobo J. D. Macrophage heterogeneity in man. A subpopulation of HLA-DR-bearing macrophages required for antigen-induced T cell activation also contains stimulators for autologous-reactive T cells. J Exp Med. 1980 Sep 1;152(3):581–593. doi: 10.1084/jem.152.3.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ramila G., Erb P. Accessory cell-dependent selection of specific T-cell functions. Nature. 1983 Aug 4;304(5925):442–445. doi: 10.1038/304442a0. [DOI] [PubMed] [Google Scholar]
  25. Roberts N. J., Jr, Steigbigel R. T. Effect of in vitro virus infection on response of human monocytes and lymphocytes to mitogen stimulation. J Immunol. 1978 Sep;121(3):1052–1058. [PubMed] [Google Scholar]
  26. Rossi G. A., Zocchi E., Sacco O., Balbi B., Ravazzoni C., Damiani G. Alveolar macrophage stimulation of T-cell proliferation in autologous mixed lymphocyte reactions. Role of HLA-DR antigens. Am Rev Respir Dis. 1986 Jan;133(1):78–82. doi: 10.1164/arrd.1986.133.1.78. [DOI] [PubMed] [Google Scholar]
  27. Smolen J. S., Sharrow S. O., Reeves J. P., Boegel W. A., Steinberg A. D. The human autologous mixed lymphocyte reaction. I. Suppression by macrophages and T cells. J Immunol. 1981 Nov;127(5):1987–1993. [PubMed] [Google Scholar]
  28. Toews G. B., Vial W. C., Dunn M. M., Guzzetta P., Nunez G., Stastny P., Lipscomb M. F. The accessory cell function of human alveolar macrophages in specific T cell proliferation. J Immunol. 1984 Jan;132(1):181–186. [PubMed] [Google Scholar]
  29. Weksler M. E., Moody C. E., Jr, Kozak R. W. The autologous mixed-lymphocyte reaction. Adv Immunol. 1981;31:271–312. doi: 10.1016/s0065-2776(08)60923-2. [DOI] [PubMed] [Google Scholar]
  30. Wewers M. D., Rennard S. I., Hance A. J., Bitterman P. B., Crystal R. G. Normal human alveolar macrophages obtained by bronchoalveolar lavage have a limited capacity to release interleukin-1. J Clin Invest. 1984 Dec;74(6):2208–2218. doi: 10.1172/JCI111647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wilde D. B., Prystowsky M. B., Beller D. I., Goldwasser E., Ihle J. N., Vogel S. N., Fitch F. W. Comparison of allogeneic and self-restricted stimulation of lymphokine production by dual-reactive cloned T cells. J Immunol. 1984 Oct;133(4):1992–1995. [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES