Abstract
Conventional immunohistochemical analysis of airway intraepithelial class II major histocompatibility complex (Ia) expression demonstrates a morphologically heterogeneous pattern of staining, suggestive of the presence of a mixed population of endogenous antigen presenting cells. Employing a novel tissue sectioning technique in conjunction with optimal surface antigen fixation, we now demonstrate that virtually all intraepithelial Ia staining throughout the respiratory tree in the normal rat, can be accounted for by a network of cells with classical dendritic cell (DC) morphology. The density of DC varies from 600-800 per mm2 epithelial surface in the large airways, to 75 per mm2 in the epithelium of the small airways of the peripheral lung. All the airway DC costain for CD4, with low-moderate expression of a variety of other leukocyte surface markers. Both chronic (eosinophilic) inflammation and acute (neutrophilic) inflammation, caused respectively by inhalation of chemical irritants in dust or aerosolised bacterial lipopolysaccharide (LPS), are shown to be accompanied by increased intraepithelial DC density in the large airways (in the order of 50%) and up to threefold increased expression of activation markers, including the beta chain of CD11/18. The kinetics of the changes in the DC network in response to LPS mirrored those of the transient neutrophil influx, suggesting that airway intraepithelial DC constitute a dynamic population which is rapidly upregulated in response to local inflammation. These findings have important theoretical implications for research on T cell activation in the context of allergic and infectious diseases in the respiratory tract.
Full Text
The Full Text of this article is available as a PDF (1.3 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ahlfors E. E., Larsson P. A., Bergstresser P. R. Langerhans cell surface densities in rat oral mucosa and human buccal mucosa. J Oral Pathol. 1985 May;14(5):390–397. doi: 10.1111/j.1600-0714.1985.tb00510.x. [DOI] [PubMed] [Google Scholar]
- Ayars G. H., Altman L. C., Frazier C. E., Chi E. Y. The toxicity of constituents of cedar and pine woods to pulmonary epithelium. J Allergy Clin Immunol. 1989 Mar;83(3):610–618. doi: 10.1016/0091-6749(89)90073-0. [DOI] [PubMed] [Google Scholar]
- Barclay A. N. Different reticular elements in rat lymphoid tissue identified by localization of Ia, Thy-1 and MRC OX 2 antigens. Immunology. 1981 Dec;44(4):727–736. [PMC free article] [PubMed] [Google Scholar]
- Bhattacharya A., Dorf M. E., Springer T. A. A shared alloantigenic determinant on Ia antigens encoded by the I-A and I-E subregions: evidence for I region gene duplication. J Immunol. 1981 Dec;127(6):2488–2495. [PubMed] [Google Scholar]
- Damoiseaux J. G., Döpp E. A., Neefjes J. J., Beelen R. H., Dijkstra C. D. Heterogeneity of macrophages in the rat evidenced by variability in determinants: two new anti-rat macrophage antibodies against a heterodimer of 160 and 95 kd (CD11/CD18). J Leukoc Biol. 1989 Dec;46(6):556–564. doi: 10.1002/jlb.46.6.556. [DOI] [PubMed] [Google Scholar]
- Dijkstra C. D., Döpp E. A., Joling P., Kraal G. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology. 1985 Mar;54(3):589–599. [PMC free article] [PubMed] [Google Scholar]
- Griffith B. P., Paradis I. L., Zeevi A., Rabinowich H., Yousem S. A., Duquesnoy R. J., Dauber J. H., Hardesty R. L. Immunologically mediated disease of the airways after pulmonary transplantation. Ann Surg. 1988 Sep;208(3):371–378. doi: 10.1097/00000658-198809000-00015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Holt P. G., McMenamin C. Defence against allergic sensitization in the healthy lung: the role of inhalation tolerance. Clin Exp Allergy. 1989 May;19(3):255–262. doi: 10.1111/j.1365-2222.1989.tb02380.x. [DOI] [PubMed] [Google Scholar]
- Holt P. G., Reid M., Britten D., Sedgwick J., Bazin H. Suppression of IgE responses by passive antigen inhalation: dissociation of local (mucosal) and systemic immunity. Cell Immunol. 1987 Feb;104(2):434–439. doi: 10.1016/0008-8749(87)90045-1. [DOI] [PubMed] [Google Scholar]
- Holt P. G., Schon-Hegrad M. A. Localization of T cells, macrophages and dendritic cells in rat respiratory tract tissue: implications for immune function studies. Immunology. 1987 Nov;62(3):349–356. [PMC free article] [PubMed] [Google Scholar]
- Holt P. G., Schon-Hegrad M. A., Oliver J., Holt B. J., McMenamin P. G. A contiguous network of dendritic antigen-presenting cells within the respiratory epithelium. Int Arch Allergy Appl Immunol. 1990;91(2):155–159. doi: 10.1159/000235107. [DOI] [PubMed] [Google Scholar]
- 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]
- Holt P. G., Schon-Hegrad M. A., Phillips M. J., McMenamin P. G. Ia-positive dendritic cells form a tightly meshed network within the human airway epithelium. Clin Exp Allergy. 1989 Nov;19(6):597–601. doi: 10.1111/j.1365-2222.1989.tb02752.x. [DOI] [PubMed] [Google Scholar]
- Kradin R. L., McCarthy K. M., Gifford J., Schneeberger E. E. Antigen-independent binding of T-cells by dendritic cells and alveolar macrophages in the rat. Am Rev Respir Dis. 1989 Jan;139(1):207–211. doi: 10.1164/ajrccm/139.1.207. [DOI] [PubMed] [Google Scholar]
- 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]
- Mayrhofer G., Holt P. G., Papadimitriou J. M. Functional characteristics of the veiled cells in afferent lymph from the rat intestine. Immunology. 1986 Jul;58(3):379–387. [PMC free article] [PubMed] [Google Scholar]
- Nicod L. P., Lipscomb M. F., Weissler J. C., Lyons C. R., Albertson J., Toews G. B. Mononuclear cells in human lung parenchyma. Characterization of a potent accessory cell not obtained by bronchoalveolar lavage. Am Rev Respir Dis. 1987 Oct;136(4):818–823. doi: 10.1164/ajrccm/136.4.818. [DOI] [PubMed] [Google Scholar]
- Robinson A. P., White T. M., Mason D. W. Macrophage heterogeneity in the rat as delineated by two monoclonal antibodies MRC OX-41 and MRC OX-42, the latter recognizing complement receptor type 3. Immunology. 1986 Feb;57(2):239–247. [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Soler P., Chollet S., Jacque C., Fukuda Y., Ferrans V. J., Basset F. Immunocytochemical characterization of pulmonary histiocytosis X cells in lung biopsies. Am J Pathol. 1985 Mar;118(3):439–451. [PMC free article] [PubMed] [Google Scholar]
- Steinman R. M., Nussenzweig M. C. Dendritic cells: features and functions. Immunol Rev. 1980;53:127–147. doi: 10.1111/j.1600-065x.1980.tb01042.x. [DOI] [PubMed] [Google Scholar]
- 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]
- Stewart G. A., Holt P. G. Submicronic airborne allergens. Med J Aust. 1985 Oct 28;143(9):426–427. doi: 10.5694/j.1326-5377.1985.tb123117.x. [DOI] [PubMed] [Google Scholar]
- Tam E. K., Calonico L. D., Nadel J. A., McDonald D. M. Globule leukocytes and mast cells in the rat trachea: their number, distribution, and response to compound 48/80 and dexamethasone. Anat Embryol (Berl) 1988;178(2):107–118. doi: 10.1007/BF02463644. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tazelaar H. D., Yousem S. A. The pathology of combined heart-lung transplantation: an autopsy study. Hum Pathol. 1988 Dec;19(12):1403–1416. doi: 10.1016/s0046-8177(88)80233-8. [DOI] [PubMed] [Google Scholar]
- Venaille T., Snella M. C., Holt P. G., Rylander R. Cell recruitment into lung wall and airways of conventional and pathogen-free guinea pigs after inhalation of endotoxin. Am Rev Respir Dis. 1989 Jun;139(6):1356–1360. doi: 10.1164/ajrccm/139.6.1356. [DOI] [PubMed] [Google Scholar]