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. 1994 Jan 1;179(1):203–212. doi: 10.1084/jem.179.1.203

Development of the airway intraepithelial dendritic cell network in the rat from class II major histocompatibility (Ia)-negative precursors: differential regulation of Ia expression at different levels of the respiratory tract

PMCID: PMC2191342  PMID: 8270865

Abstract

The relative inefficiency of respiratory mucosal immune function during infancy is generally attributed to the immaturity of the neonatal T cell system. However, immune competence in the adult lung has recently been shown to be closely linked to the functional capacity of local networks of intraepithelial dendritic cells (DC). This study examines the density and distribution of these DC throughout the neonatal respiratory tract in rats, focusing particularly on microenvironmental regulation of their class II major histocompatibility complex (MHC) (Ia) expression. In animals housed under dust-controlled conditions, airway epithelial and alveolar Ia+ DC detectable by immunostaining with the monoclonal antibody (mAb) Ox6 are usually not seen until day 2-3 after birth, and adult-equivalent staining patterns are not observed until after weaning. In contrast, the mAb Ox62 detects large numbers of DC in fetal, infant, and adult rat airway epithelium. Costaining of these Ox62+ DC with Ox6 is rare in the neonate and increases progressively throughout infancy, and by weaning Ia+ DC comprised, on average, 65% of the overall intraepithelial DC population. In infant rats, Ia+ DC are observed first at the base of the nasal turbinates, sites of maximum exposure to inhaled particulates, suggesting that their maturation is driven in part by inflammatory stimuli. Consistent with this suggestion, densitometric analysis of Ia staining intensity of individual DC demonstrates that by 2-3 d after birth, Ia expression by nasal epithelial DC was comparable with that of Iahigh epidermal Langerhans cells in adjacent facial skin, at a time when expression by tracheal epithelial DC was 7-10-fold lower. Additionally, the rate of postnatal appearance of Iahigh DC in the airway epithelium was increased by administration of interferon gamma, and decreased by exposure of infant rats to aerosolized steroid. These findings collectively suggest that Ia expression by neonatal respiratory tract DC is locally controlled and can be upregulated by mediators that are produced within the lung and airway epithelium in response to inhalation of proinflammatory stimuli. It was also noted that Ialow neonatal airway DC expressed adult equivalent levels of class I MHC, which suggests differences in capacity to prime for CD8(+)-dependent versus CD4(+)-dependent immunity to inhaled pathogens, during the early postnatal period.

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Selected References

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  1. Brenan M., Puklavec M. The MRC OX-62 antigen: a useful marker in the purification of rat veiled cells with the biochemical properties of an integrin. J Exp Med. 1992 Jun 1;175(6):1457–1465. doi: 10.1084/jem.175.6.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. David-Watine B., Israël A., Kourilsky P. The regulation and expression of MHC class I genes. Immunol Today. 1990 Aug;11(8):286–292. doi: 10.1016/0167-5699(90)90114-o. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Hanson D. G. Ontogeny of orally induced tolerance to soluble proteins in mice. I. Priming and tolerance in newborns. J Immunol. 1981 Oct;127(4):1518–1524. [PubMed] [Google Scholar]
  6. Heufler C., Koch F., Schuler G. Granulocyte/macrophage colony-stimulating factor and interleukin 1 mediate the maturation of murine epidermal Langerhans cells into potent immunostimulatory dendritic cells. J Exp Med. 1988 Feb 1;167(2):700–705. doi: 10.1084/jem.167.2.700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Holt P. G., Clough J. B., Holt B. J., Baron-Hay M. J., Rose A. H., Robinson B. W., Thomas W. R. Genetic 'risk' for atopy is associated with delayed postnatal maturation of T-cell competence. Clin Exp Allergy. 1992 Dec;22(12):1093–1099. doi: 10.1111/j.1365-2222.1992.tb00135.x. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Holt P. G., Degebrodt A., Venaille T., O'Leary C., Krska K., Flexman J., Farrell H., Shellam G., Young P., Penhale J. Preparation of interstitial lung cells by enzymatic digestion of tissue slices: preliminary characterization by morphology and performance in functional assays. Immunology. 1985 Jan;54(1):139–147. [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. Regulation of antigen-presenting cell function(s) in lung and airway tissues. Eur Respir J. 1993 Jan;6(1):120–129. [PubMed] [Google Scholar]
  12. Holt P. G., Schon-Hegrad M. A., McMenamin P. G. Dendritic cells in the respiratory tract. Int Rev Immunol. 1990;6(2-3):139–149. doi: 10.3109/08830189009056625. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Holt P. G., Vines J., Britten D. Suppression of IgE responses by antigen inhalation: failure of tolerance mechanism(s) in newborn rats. Immunology. 1988 Apr;63(4):591–593. [PMC free article] [PubMed] [Google Scholar]
  15. Inaba K., Kitaura M., Kato T., Watanabe Y., Kawade Y., Muramatsu S. Contrasting effect of alpha/beta- and gamma-interferons on expression of macrophage Ia antigens. J Exp Med. 1986 Apr 1;163(4):1030–1035. doi: 10.1084/jem.163.4.1030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kitaura M., Kato T., Inaba K., Watanabe Y., Kawade Y., Muramatsu S. Ontogeny of 'macrophage' function. VI. Down-regulation for Ia-expression of newborn mouse macrophages by endogenous beta-interferon. Dev Comp Immunol. 1988 Summer;12(3):645–655. doi: 10.1016/0145-305x(88)90080-8. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Mayrhofer G., Pugh C. W., Barclay A. N. The distribution, ontogeny and origin in the rat of Ia-positive cells with dendritic morphology and of Ia antigen in epithelia, with special reference to the intestine. Eur J Immunol. 1983 Feb;13(2):112–122. doi: 10.1002/eji.1830130206. [DOI] [PubMed] [Google Scholar]
  20. McCarthy K. M., Gong J. L., Telford J. R., Schneeberger E. E. Ontogeny of Ia+ accessory cells in fetal and newborn rat lung. Am J Respir Cell Mol Biol. 1992 Mar;6(3):349–356. doi: 10.1165/ajrcmb/6.3.349. [DOI] [PubMed] [Google Scholar]
  21. McMenamin C., Holt P. G. The natural immune response to inhaled soluble protein antigens involves major histocompatibility complex (MHC) class I-restricted CD8+ T cell-mediated but MHC class II-restricted CD4+ T cell-dependent immune deviation resulting in selective suppression of immunoglobulin E production. J Exp Med. 1993 Sep 1;178(3):889–899. doi: 10.1084/jem.178.3.889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Murgita R. A., Wigzell H. Regulation of immune functions in the fetus and newborn. Prog Allergy. 1981;29:54–133. [PubMed] [Google Scholar]
  23. Romani N., Schuler G., Fritsch P. Ontogeny of Ia-positive and Thy-1-positive leukocytes of murine epidermis. J Invest Dermatol. 1986 Feb;86(2):129–133. doi: 10.1111/1523-1747.ep12284135. [DOI] [PubMed] [Google Scholar]
  24. Schon-Hegrad M. A., Oliver J., McMenamin P. G., Holt P. G. Studies on the density, distribution, and surface phenotype of intraepithelial class II major histocompatibility complex antigen (Ia)-bearing dendritic cells (DC) in the conducting airways. J Exp Med. 1991 Jun 1;173(6):1345–1356. doi: 10.1084/jem.173.6.1345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schuler G., Steinman R. M. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J Exp Med. 1985 Mar 1;161(3):526–546. doi: 10.1084/jem.161.3.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Simecka J. W., Davis J. K., Cassell G. H. Distribution of Ia antigens and T lymphocyte subpopulations in rat lungs. Immunology. 1986 Jan;57(1):93–98. [PMC free article] [PubMed] [Google Scholar]
  27. Strobel S., Ferguson A. Immune responses to fed protein antigens in mice. 3. Systemic tolerance or priming is related to age at which antigen is first encountered. Pediatr Res. 1984 Jul;18(7):588–594. doi: 10.1203/00006450-198407000-00004. [DOI] [PubMed] [Google Scholar]
  28. Wara D. W., Barrett D. J. Cell-mediated immunity in the newborn: clinical aspects. Pediatrics. 1979 Nov;64(5 Pt 2 Suppl):822–828. [PubMed] [Google Scholar]
  29. Wilson C. B. Immunologic basis for increased susceptibility of the neonate to infection. J Pediatr. 1986 Jan;108(1):1–12. doi: 10.1016/s0022-3476(86)80761-2. [DOI] [PubMed] [Google Scholar]
  30. van Rees E. P., van der Ende M. B., Sminia T. Ontogeny of macrophage subpopulations and Ia-positive dendritic cells in pulmonary tissue of the rat. Cell Tissue Res. 1991 Feb;263(2):367–373. doi: 10.1007/BF00318778. [DOI] [PubMed] [Google Scholar]

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