Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1995 Jan;84(1):142–147.

Alveolar macrophages from humans and rodents selectively inhibit T-cell proliferation but permit T-cell activation and cytokine secretion.

J W Upham 1, D H Strickland 1, N Bilyk 1, B W Robinson 1, P G Holt 1
PMCID: PMC1415174  PMID: 7534261

Abstract

Alveolar macrophages (AM) are thought to play a key role in the regulation of immune responses within the lung. While it is well established that AM inhibit T-cell proliferation in vitro, it is unclear whether other aspects of the T-cell activation process are also inhibited. The present study demonstrates that AM from rat, mouse and human differ markedly in the potency with which they inhibit mitogen-induced T-cell proliferation, although in humans the degree of inhibition approaches that observed in the animal systems, if antigen (as opposed to mitogen) is employed as the T-cell activating agent. Rodent and human AM also differ in the mechanisms employed to achieve this inhibition; rodent AM appear to utilize reactive nitrogen intermediates, while this does not appear to be the case for human AM. Despite these differences, T cells stimulated in the presence of AM display a similar phenotype in all species examined, i.e. CD3 down-modulation, up-regulation of interleukin-2 receptor (IL-2R) expression and IL-2 production, but inability to respond to IL-2. Thus, AM appear to allow T-cell activation and expression of T-cell effector function, while selectively inhibiting T-cell proliferation.

Full text

PDF

Selected References

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

  1. Albina J. E., Abate J. A., Henry W. L., Jr Nitric oxide production is required for murine resident peritoneal macrophages to suppress mitogen-stimulated T cell proliferation. Role of IFN-gamma in the induction of the nitric oxide-synthesizing pathway. J Immunol. 1991 Jul 1;147(1):144–148. [PubMed] [Google Scholar]
  2. Bilyk N., Mackenzie J. S., Papadimitriou J. M., Holt P. G. Functional studies on macrophage populations in the airways and the lung wall of SPF mice in the steady-state and during respiratory virus infection. Immunology. 1988 Nov;65(3):417–425. [PMC free article] [PubMed] [Google Scholar]
  3. Cameron M. L., Granger D. L., Weinberg J. B., Kozumbo W. J., Koren H. S. Human alveolar and peritoneal macrophages mediate fungistasis independently of L-arginine oxidation to nitrite or nitrate. Am Rev Respir Dis. 1990 Dec;142(6 Pt 1):1313–1319. doi: 10.1164/ajrccm/142.6_Pt_1.1313. [DOI] [PubMed] [Google Scholar]
  4. Daynes R. A., Araneo B. A., Dowell T. A., Huang K., Dudley D. Regulation of murine lymphokine production in vivo. III. The lymphoid tissue microenvironment exerts regulatory influences over T helper cell function. J Exp Med. 1990 Apr 1;171(4):979–996. doi: 10.1084/jem.171.4.979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Fu Y., Blankenhorn E. P. Nitric oxide-induced anti-mitogenic effects in high and low responder rat strains. J Immunol. 1992 Apr 1;148(7):2217–2222. [PubMed] [Google Scholar]
  7. Holt P. G. Alveolar macrophages. IV. Interspecies differences in activity in proliferating lymphocyte cultures. Cell Immunol. 1980 Mar 1;50(1):210–215. doi: 10.1016/0008-8749(80)90020-9. [DOI] [PubMed] [Google Scholar]
  8. Holt P. G. Down-regulation of immune responses in the lower respiratory tract: the role of alveolar macrophages. Clin Exp Immunol. 1986 Feb;63(2):261–270. [PMC free article] [PubMed] [Google Scholar]
  9. Holt P. G. Regulation of antigen-presenting cell function(s) in lung and airway tissues. Eur Respir J. 1993 Jan;6(1):120–129. [PubMed] [Google Scholar]
  10. Holt P. G., Schon-Hegrad M. A., Oliver J. MHC class II antigen-bearing dendritic cells in pulmonary tissues of the rat. Regulation of antigen presentation activity by endogenous macrophage populations. J Exp Med. 1988 Feb 1;167(2):262–274. doi: 10.1084/jem.167.2.262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Huot A. E., Moore A. L., Roberts J. D., Hacker M. P. Nitric oxide modulates lymphocyte proliferation but not secretion of IL-2. Immunol Invest. 1993 Jun;22(4):319–327. doi: 10.3109/08820139309063411. [DOI] [PubMed] [Google Scholar]
  12. Kawabe T., Isobe K. I., Hasegawa Y., Nakashima I., Shimokata K. Immunosuppressive activity induced by nitric oxide in culture supernatant of activated rat alveolar macrophages. Immunology. 1992 May;76(1):72–78. [PMC free article] [PubMed] [Google Scholar]
  13. Kobzik L., Bredt D. S., Lowenstein C. J., Drazen J., Gaston B., Sugarbaker D., Stamler J. S. Nitric oxide synthase in human and rat lung: immunocytochemical and histochemical localization. Am J Respir Cell Mol Biol. 1993 Oct;9(4):371–377. doi: 10.1165/ajrcmb/9.4.371. [DOI] [PubMed] [Google Scholar]
  14. Marletta M. A., Yoon P. S., Iyengar R., Leaf C. D., Wishnok J. S. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry. 1988 Nov 29;27(24):8706–8711. doi: 10.1021/bi00424a003. [DOI] [PubMed] [Google Scholar]
  15. Mason D. W., Arthur R. P., Dallman M. J., Green J. R., Spickett G. P., Thomas M. L. Functions of rat T-lymphocyte subsets isolated by means of monoclonal antibodies. Immunol Rev. 1983;74:57–82. doi: 10.1111/j.1600-065x.1983.tb01084.x. [DOI] [PubMed] [Google Scholar]
  16. McCombs C. C., Michalski J. P., Westerfield B. T., Light R. W. Human alveolar macrophages suppress the proliferative response of peripheral blood lymphocytes. Chest. 1982 Sep;82(3):266–271. doi: 10.1378/chest.82.3.266. [DOI] [PubMed] [Google Scholar]
  17. Merryman P. F., Clancy R. M., He X. Y., Abramson S. B. Modulation of human T cell responses by nitric oxide and its derivative, S-nitrosoglutathione. Arthritis Rheum. 1993 Oct;36(10):1414–1422. doi: 10.1002/art.1780361014. [DOI] [PubMed] [Google Scholar]
  18. Moore S. A., Strieter R. M., Rolfe M. W., Standiford T. J., Burdick M. D., Kunkel S. L. Expression and regulation of human alveolar macrophage-derived interleukin-1 receptor antagonist. Am J Respir Cell Mol Biol. 1992 Jun;6(6):569–575. doi: 10.1165/ajrcmb/6.6.569. [DOI] [PubMed] [Google Scholar]
  19. Nicolls M. R., Aversa G. G., Pearce N. W., Spinelli A., Berger M. F., Gurley K. E., Hall B. M. Induction of long-term specific tolerance to allografts in rats by therapy with an anti-CD3-like monoclonal antibody. Transplantation. 1993 Mar;55(3):459–468. doi: 10.1097/00007890-199303000-00001. [DOI] [PubMed] [Google Scholar]
  20. Paine R., 3rd, Mody C. H., Chavis A., Spahr M. A., Turka L. A., Toews G. B. Alveolar epithelial cells block lymphocyte proliferation in vitro without inhibiting activation. Am J Respir Cell Mol Biol. 1991 Sep;5(3):221–229. doi: 10.1165/ajrcmb/5.3.221. [DOI] [PubMed] [Google Scholar]
  21. Paliogianni F., Ahuja S. S., Balow J. P., Balow J. E., Boumpas D. T. Novel mechanism for inhibition of human T cells by glucocorticoids. Glucocorticoids inhibit signal transduction through IL-2 receptor. J Immunol. 1993 Oct 15;151(8):4081–4089. [PubMed] [Google Scholar]
  22. Paterson D. J., Jefferies W. A., Green J. R., Brandon M. R., Corthesy P., Puklavec M., Williams A. F. Antigens of activated rat T lymphocytes including a molecule of 50,000 Mr detected only on CD4 positive T blasts. Mol Immunol. 1987 Dec;24(12):1281–1290. doi: 10.1016/0161-5890(87)90122-2. [DOI] [PubMed] [Google Scholar]
  23. Rich E. A., Cooper C., Toossi Z., Leonard M. L., Stucky R. M., Wiblin R. T., Ellner J. J. Requirement for cell-to-cell contact for the immunosuppressive activity of human alveolar macrophages. Am J Respir Cell Mol Biol. 1991 Mar;4(3):287–294. doi: 10.1165/ajrcmb/4.3.287. [DOI] [PubMed] [Google Scholar]
  24. Robinson B. W., James A., Rose A. H., Sterrett G. F., Musk A. W. Bronchoalveolar lavage sampling of airway and alveolar cells. Br J Dis Chest. 1988 Jan;82(1):45–55. doi: 10.1016/0007-0971(88)90007-1. [DOI] [PubMed] [Google Scholar]
  25. Schneemann M., Schoedon G., Hofer S., Blau N., Guerrero L., Schaffner A. Nitric oxide synthase is not a constituent of the antimicrobial armature of human mononuclear phagocytes. J Infect Dis. 1993 Jun;167(6):1358–1363. doi: 10.1093/infdis/167.6.1358. [DOI] [PubMed] [Google Scholar]
  26. Strickland D. H., Thepen T., Kees U. R., Kraal G., Holt P. G. Regulation of T-cell function in lung tissue by pulmonary alveolar macrophages. Immunology. 1993 Oct;80(2):266–272. [PMC free article] [PubMed] [Google Scholar]
  27. Suzuki G., Kawase Y., Koyasu S., Yahara I., Kobayashi Y., Schwartz R. H. Antigen-induced suppression of the proliferative response of T cell clones. J Immunol. 1988 Mar 1;140(5):1359–1365. [PubMed] [Google Scholar]
  28. Thepen T., McMenamin C., Girn B., Kraal G., Holt P. G. Regulation of IgE production in pre-sensitized animals: in vivo elimination of alveolar macrophages preferentially increases IgE responses to inhaled allergen. Clin Exp Allergy. 1992 Dec;22(12):1107–1114. doi: 10.1111/j.1365-2222.1992.tb00137.x. [DOI] [PubMed] [Google Scholar]
  29. Thepen T., Van Rooijen N., Kraal G. Alveolar macrophage elimination in vivo is associated with an increase in pulmonary immune response in mice. J Exp Med. 1989 Aug 1;170(2):499–509. doi: 10.1084/jem.170.2.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tomonari K. A rat antibody against a structure functionally related to the mouse T-cell receptor/T3 complex. Immunogenetics. 1988;28(6):455–458. doi: 10.1007/BF00355379. [DOI] [PubMed] [Google Scholar]
  31. al-Ramadi B. K., Meissler J. J., Jr, Huang D., Eisenstein T. K. Immunosuppression induced by nitric oxide and its inhibition by interleukin-4. Eur J Immunol. 1992 Sep;22(9):2249–2254. doi: 10.1002/eji.1830220911. [DOI] [PubMed] [Google Scholar]

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

RESOURCES