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. 1995 Apr 1;181(4):1275–1283. doi: 10.1084/jem.181.4.1275

The antigen-presenting activities of Ia+ dendritic cells shift dynamically from lung to lymph node after an airway challenge with soluble antigen

PMCID: PMC2191960  PMID: 7699319

Abstract

Dendritic cells (DC) are widely distributed in the lung where they are distinguished by their morphology and class II major histocompatibility complex (Ia) antigen expression. Although a role for DC as pulmonary antigen-presenting cell (APC) has been suggested, little is currently known concerning how these cells respond to inhaled antigens in vivo. Hen-egg lysozyme (HEL) was injected intratracheally into Lewis rats; DC were subsequently purified from the lung and regional lymph nodes (LN) at intervals of up to 14 d and examined for their ability to stimulate the proliferation of HEL-immune T cells in vitro in the absence of added HEL. Pulmonary DC displayed APC activities at 3 h and for up to 7 d after the injection of antigen. Dendritic cells in the draining hilar LN showed APC activities that appeared at 24 h, peaked at day 3, and then diminished progressively. After the primary sensitization, HEL- immune T cells were detected in hilar LN but not in the lung. A second airway challenge with HEL at day 14 yielded an antigen-specific pulmonary immune response, characterized histologically by the accumulation of mononuclear cells around lung venules. We conclude that APC activities shift from lung to lymph node during the response to inhaled antigen.

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Selected References

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  1. Ahlstedt S., Smedegård G., Nygren H., Björkstén B. Immune responses in rats sensitized with aerosolized antigen. Antibody formation, lymphoblastic responses and mast cell and mucous cell development related to bronchial reactivity. Int Arch Allergy Appl Immunol. 1983;72(1):71–78. doi: 10.1159/000234843. [DOI] [PubMed] [Google Scholar]
  2. Butler J. E., Swanson P. A., Richerson H. B., Ratajczak H. V., Richards D. W., Suelzer M. T. The local and systemic IgA and IgG antibody responses of rabbits to a soluble inhaled antigen: measurement of responses in a model of acute hypersensitivity pneumonitis. Am Rev Respir Dis. 1982 Jul;126(1):80–85. doi: 10.1164/arrd.1982.126.1.80. [DOI] [PubMed] [Google Scholar]
  3. Gong J. L., McCarthy K. M., Telford J., Tamatani T., Miyasaka M., Schneeberger E. E. Intraepithelial airway dendritic cells: a distinct subset of pulmonary dendritic cells obtained by microdissection. J Exp Med. 1992 Mar 1;175(3):797–807. doi: 10.1084/jem.175.3.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Havenith C. E., Breedijk A. J., Betjes M. G., Calame W., Beelen R. H., Hoefsmit E. C. T cell priming in situ by intratracheally instilled antigen-pulsed dendritic cells. Am J Respir Cell Mol Biol. 1993 Mar;8(3):319–324. doi: 10.1165/ajrcmb/8.3.319. [DOI] [PubMed] [Google Scholar]
  5. Havenith C. E., Breedijk A. J., Calame W., Beelen R. H., Hoefsmit E. C. Antigen specific T cell priming in vivo by intratracheal injection of antigen presenting cells. Adv Exp Med Biol. 1993;329:571–575. doi: 10.1007/978-1-4615-2930-9_95. [DOI] [PubMed] [Google Scholar]
  6. Henney C. S., Waldman R. H. Cell-mediated immunity shown by lymphocytes from the respiratory tract. Science. 1970 Aug 14;169(3946):696–697. doi: 10.1126/science.169.3946.696. [DOI] [PubMed] [Google Scholar]
  7. Holt P. G., Degebrodt A., O'Leary C., Krska K., Plozza T. T cell activation by antigen-presenting cells from lung tissue digests: suppression by endogenous macrophages. Clin Exp Immunol. 1985 Dec;62(3):586–593. [PMC free article] [PubMed] [Google Scholar]
  8. Holt P. G., Haining S., Nelson D. J., Sedgwick J. D. Origin and steady-state turnover of class II MHC-bearing dendritic cells in the epithelium of the conducting airways. J Immunol. 1994 Jul 1;153(1):256–261. [PubMed] [Google Scholar]
  9. Holt P. G., Oliver J., Bilyk N., McMenamin C., McMenamin P. G., Kraal G., Thepen T. Downregulation of the antigen presenting cell function(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages. J Exp Med. 1993 Feb 1;177(2):397–407. doi: 10.1084/jem.177.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Holt P. G., Oliver J., McMenamin C., Schon-Hegrad M. A. Studies on the surface phenotype and functions of dendritic cells in parenchymal lung tissue of the rat. Immunology. 1992 Apr;75(4):582–587. [PMC free article] [PubMed] [Google Scholar]
  11. Holt P. G. Pulmonary dendritic cell populations. Adv Exp Med Biol. 1993;329:557–562. doi: 10.1007/978-1-4615-2930-9_93. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Klinkert W. E., LaBadie J. H., Bowers W. E. Accessory and stimulating properties of dendritic cells and macrophages isolated from various rat tissues. J Exp Med. 1982 Jul 1;156(1):1–19. doi: 10.1084/jem.156.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kradin R. L., McCarthy K. M., Dailey C. I., Burdeshaw A., Kurnick J. T., Schneeberger E. E. The poor accessory cell function of macrophages in the rat may reflect their inability to form clusters with T cells. Clin Immunol Immunopathol. 1987 Sep;44(3):348–363. doi: 10.1016/0090-1229(87)90079-1. [DOI] [PubMed] [Google Scholar]
  15. Kradin R. L., McCarthy K. M., Xia W. J., Lazarus D., Schneeberger E. E. Accessory cells of the lung. I. Interferon-gamma increases Ia+ dendritic cells in the lung without augmenting their accessory activities. Am J Respir Cell Mol Biol. 1991 Mar;4(3):210–218. doi: 10.1165/ajrcmb/4.3.210. [DOI] [PubMed] [Google Scholar]
  16. Kradin R. L., Xia W., McCarthy K., Schneeberger E. E. FcR+/- subsets of Ia+ pulmonary dendritic cells in the rat display differences in their abilities to provide accessory co-stimulation for naive (OX-22+) and sensitized (OX-22-) T cells. Am J Pathol. 1993 Mar;142(3):811–819. [PMC free article] [PubMed] [Google Scholar]
  17. Lipscomb M. F., Lyons C. R., O'Hara R. M., Jr, Stein-Streilein J. The antigen-induced selective recruitment of specific T lymphocytes to the lung. J Immunol. 1982 Jan;128(1):111–115. [PubMed] [Google Scholar]
  18. Liu M. C., Ishizaka K., Plaut M. T lymphocyte responses of murine lung: immunization with alloantigen induces accumulation of cytotoxic and other T lymphocytes in the lung. J Immunol. 1982 Dec;129(6):2653–2661. [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. Macatonia S. E., Knight S. C., Edwards A. J., Griffiths S., Fryer P. Localization of antigen on lymph node dendritic cells after exposure to the contact sensitizer fluorescein isothiocyanate. Functional and morphological studies. J Exp Med. 1987 Dec 1;166(6):1654–1667. doi: 10.1084/jem.166.6.1654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mackay C. R., Marston W. L., Dudler L. Naive and memory T cells show distinct pathways of lymphocyte recirculation. J Exp Med. 1990 Mar 1;171(3):801–817. doi: 10.1084/jem.171.3.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Marathias K. P., Preffer F. I., Pinto C., Kradin R. L. Most human pulmonary infiltrating lymphocytes display the surface immune phenotype and functional responses of sensitized T cells. Am J Respir Cell Mol Biol. 1991 Nov;5(5):470–476. doi: 10.1165/ajrcmb/5.5.470. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. McWilliam A. S., Nelson D., Thomas J. A., Holt P. G. Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces. J Exp Med. 1994 Apr 1;179(4):1331–1336. doi: 10.1084/jem.179.4.1331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Platt J. L., Grant B. W., Eddy A. A., Michael A. F. Immune cell populations in cutaneous delayed-type hypersensitivity. J Exp Med. 1983 Oct 1;158(4):1227–1242. doi: 10.1084/jem.158.4.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rich E. A., Tweardy D. J., Fujiwara H., Ellner J. J. Spectrum of immunoregulatory functions and properties of human alveolar macrophages. Am Rev Respir Dis. 1987 Aug;136(2):258–265. doi: 10.1164/ajrccm/136.2.258. [DOI] [PubMed] [Google Scholar]
  27. Rochester C. L., Goodell E. M., Stoltenborg J. K., Bowers W. E. Dendritic cells from rat lung are potent accessory cells. Am Rev Respir Dis. 1988 Jul;138(1):121–128. doi: 10.1164/ajrccm/138.1.121. [DOI] [PubMed] [Google Scholar]
  28. Sertl K., Takemura T., Tschachler E., Ferrans V. J., Kaliner M. A., Shevach E. M. Dendritic cells with antigen-presenting capability reside in airway epithelium, lung parenchyma, and visceral pleura. J Exp Med. 1986 Feb 1;163(2):436–451. doi: 10.1084/jem.163.2.436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Steinman R. M., Cohn Z. A. Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro. J Exp Med. 1974 Feb 1;139(2):380–397. doi: 10.1084/jem.139.2.380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Steinman R. M. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:271–296. doi: 10.1146/annurev.iy.09.040191.001415. [DOI] [PubMed] [Google Scholar]
  31. Taylor F. G., Bourne F. J. Enhanced lung clearance of antigen in immunised mice. Int Arch Allergy Appl Immunol. 1985;76(3):243–250. doi: 10.1159/000233699. [DOI] [PubMed] [Google Scholar]
  32. Willoughby J. B., Willoughby W. F. In vivo responses to inhaled proteins. I. Quantitative analysis of antigen uptake, fate, and immunogenicity in a rabbit model system. J Immunol. 1977 Dec;119(6):2137–2146. [PubMed] [Google Scholar]
  33. Witmer-Pack M. D., Olivier W., Valinsky J., Schuler G., Steinman R. M. Granulocyte/macrophage colony-stimulating factor is essential for the viability and function of cultured murine epidermal Langerhans cells. J Exp Med. 1987 Nov 1;166(5):1484–1498. doi: 10.1084/jem.166.5.1484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Xia W. J., Schneeberger E. E., McCarthy K., Kradin R. L. Accessory cells of the lung. II. Ia+ pulmonary dendritic cells display cell surface antigen heterogeneity. Am J Respir Cell Mol Biol. 1991 Sep;5(3):276–283. doi: 10.1165/ajrcmb/5.3.276. [DOI] [PubMed] [Google Scholar]

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