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. 1988 Feb 1;167(2):632–645. doi: 10.1084/jem.167.2.632

Migration patterns of dendritic cells in the mouse. Traffic from the blood, and T cell-dependent and -independent entry to lymphoid tissues

PMCID: PMC2188851  PMID: 3258009

Abstract

Dendritic cells (DC) are critical accessory cells for primary immune responses and they may be important stimulators of transplantation reactions, but little is known of their traffic into the tissues. We have studied the migration of purified splenic DC and T lymphocytes, labeled with 111Indium-tropolone, in syngeneic and allogeneic mice. First we demonstrate that DC can migrate from the blood into some lymphoid and nonlymphoid tissues. Immediately after intravenous administration, radio-labeled DC were sequestered in the lungs, but they actively migrated into the liver and spleen and reached equilibrium levels between 3 and 24 h after transfer. At least half of the radiolabel accumulated in the liver, but the spleen was the principal site of DC localization in terms of specific activity (radiolabel per weight of tissue). DC were unable to enter Peyer's patches, or mesenteric and other peripheral lymph nodes from the bloodstream. This was also true in splenectomized recipients, where the otherwise spleen-seeking DC were quantitatively diverted to the liver. In contrast, T cells homed readily to the spleen and lymph nodes of normal mice and increased numbers were present in these tissues in splenectomized mice. Thus, unlike T cells, DC cannot recirculate from blood to lymph via the nodes. We then show that migration of DC from the blood into the spleen is dependent on the presence of T cells: DC did not enter the spleens of nude mice, but when they were reconstituted with T cells the numbers entering the spleen resembled those in euthymic mice. In nude mice, as in splenectomized recipients, the DC that would normally enter the spleen were quantitatively diverted to the liver. These findings suggest that there is a spleen- liver equilibrium for DC, that may be akin to that existing between spleen and lymph node for T cells. Finally, we followed the traffic of radiolabeled DC via the afferent lymphatics after subcutaneous footpad inoculation. DC accumulated in the popliteal nodes but did not migrate further to the inguinal nodes. There was no difference between euthymic and nude mice, showing that unlike traffic to the spleen, this route probably does not require T cells. These migration patterns were not affected by major histocompatibility barriers, and were only seen with viable, but not glutaraldehyde-fixed, DC.(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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  1. Austyn J. M., Gordon S. F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol. 1981 Oct;11(10):805–815. doi: 10.1002/eji.1830111013. [DOI] [PubMed] [Google Scholar]
  2. Austyn J. M., Kupiec-Weglinski J. W., Hankins D. F., Morris P. J. Migration patterns of dendritic cells in the mouse. Homing to T cell-dependent areas of spleen, and binding within marginal zone. J Exp Med. 1988 Feb 1;167(2):646–651. doi: 10.1084/jem.167.2.646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Austyn J. M. Lymphoid dendritic cells. Immunology. 1987 Oct;62(2):161–170. [PMC free article] [PubMed] [Google Scholar]
  4. Austyn J. M., Steinman R. M., Weinstein D. E., Granelli-Piperno A., Palladino M. A. Dendritic cells initiate a two-stage mechanism for T lymphocyte proliferation. J Exp Med. 1983 Apr 1;157(4):1101–1115. doi: 10.1084/jem.157.4.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coffman R. L., Weissman I. L. A monoclonal antibody that recognizes B cells and B cell precursors in mice. J Exp Med. 1981 Feb 1;153(2):269–279. doi: 10.1084/jem.153.2.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Coffman R. L., Weissman I. L. B220: a B cell-specific member of th T200 glycoprotein family. Nature. 1981 Feb 19;289(5799):681–683. doi: 10.1038/289681a0. [DOI] [PubMed] [Google Scholar]
  7. Danpure H. J., Osman S., Brady F. The labelling of blood cells in plasma with 111In-tropolonate. Br J Radiol. 1982 Mar;55(651):247–249. doi: 10.1259/0007-1285-55-651-247. [DOI] [PubMed] [Google Scholar]
  8. Dewanjee M. K., Rao S. A., Didisheim P. Indium-111 tropolone, a new high-affinity platelet label: preparation and evaluation of labeling parameters. J Nucl Med. 1981 Nov;22(11):981–987. [PubMed] [Google Scholar]
  9. Dialynas D. P., Quan Z. S., Wall K. A., Pierres A., Quintáns J., Loken M. R., Pierres M., Fitch F. W. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [PubMed] [Google Scholar]
  10. Faustman D. L., Steinman R. M., Gebel H. M., Hauptfeld V., Davie J. M., Lacy P. E. Prevention of rejection of murine islet allografts by pretreatment with anti-dendritic cell antibody. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3864–3868. doi: 10.1073/pnas.81.12.3864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Forbes R. D., Parfrey N. A., Gomersall M., Darden A. G., Guttmann R. D. Dendritic cell-lymphoid cell aggregation and major histocompatibility antigen expression during rat cardiac allograft rejection. J Exp Med. 1986 Oct 1;164(4):1239–1258. doi: 10.1084/jem.164.4.1239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. GOWANS J. L., KNIGHT E. J. THE ROUTE OF RE-CIRCULATION OF LYMPHOCYTES IN THE RAT. Proc R Soc Lond B Biol Sci. 1964 Jan 14;159:257–282. doi: 10.1098/rspb.1964.0001. [DOI] [PubMed] [Google Scholar]
  13. Goldschneider I., McGregor D. D. Migration of lymphocytes and thymocytes in the rat. II. Circulation of lymphocytes and thymocytes from blood to lymph. Lab Invest. 1968 Apr;18(4):397–406. [PubMed] [Google Scholar]
  14. Gray D., MacLennan I. C., Bazin H., Khan M. Migrant mu+ delta+ and static mu+ delta- B lymphocyte subsets. Eur J Immunol. 1982 Jul;12(7):564–569. doi: 10.1002/eji.1830120707. [DOI] [PubMed] [Google Scholar]
  15. Hart D. N., Fabre J. W. Demonstration and characterization of Ia-positive dendritic cells in the interstitial connective tissues of rat heart and other tissues, but not brain. J Exp Med. 1981 Aug 1;154(2):347–361. doi: 10.1084/jem.154.2.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hendriks H. R., Eestermans I. L. Disappearance and reappearance of high endothelial venules and immigrating lymphocytes in lymph nodes deprived of afferent lymphatic vessels: a possible regulatory role of macrophages in lymphocyte migration. Eur J Immunol. 1983 Aug;13(8):663–669. doi: 10.1002/eji.1830130811. [DOI] [PubMed] [Google Scholar]
  17. Inaba K., Steinman R. M. Accessory cell-T lymphocyte interactions. Antigen-dependent and -independent clustering. J Exp Med. 1986 Feb 1;163(2):247–261. doi: 10.1084/jem.163.2.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Knight S. C., Mertin J., Stackpoole A., Clark J. Induction of immune responses in vivo with small numbers of veiled (dendritic) cells. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6032–6035. doi: 10.1073/pnas.80.19.6032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kupiec-Weglinski J. W., Bordes-Aznar J., Clason A. E., Duarte A. J., Araneda D., Carpenter C. B., Strom T. B., Tilney N. L. Migration patterns of lymphocytes in untreated and immunologically manipulated recipients of organ allografts. Transplantation. 1982 Jun;33(6):593–598. doi: 10.1097/00007890-198206000-00005. [DOI] [PubMed] [Google Scholar]
  20. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  21. Macatonia S. E., Edwards A. J., Knight S. C. Dendritic cells and the initiation of contact sensitivity to fluorescein isothiocyanate. Immunology. 1986 Dec;59(4):509–514. [PMC free article] [PubMed] [Google Scholar]
  22. Peugh W. N., Austyn J. M., Carter N. P., Wood K. J., Morris P. J. Inability of dendritic cells to prevent the blood transfusion effect in a mouse cardiac allograft model. Transplantation. 1987 Nov;44(5):706–711. doi: 10.1097/00007890-198711000-00021. [DOI] [PubMed] [Google Scholar]
  23. Pugh C. W., MacPherson G. G., Steer H. W. Characterization of nonlymphoid cells derived from rat peripheral lymph. J Exp Med. 1983 Jun 1;157(6):1758–1779. doi: 10.1084/jem.157.6.1758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rolstad B., Herberman R. B., Reynolds C. W. Natural killer cell activity in the rat. V. The circulation patterns and tissue localization of peripheral blood large granular lymphocytes (LGL). J Immunol. 1986 Apr 15;136(8):2800–2808. [PubMed] [Google Scholar]
  25. Sarmiento M., Glasebrook A. L., Fitch F. W. IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J Immunol. 1980 Dec;125(6):2665–2672. [PubMed] [Google Scholar]
  26. 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]
  27. Sherwood R. A., Brent L., Rayfield L. S. Presentation of alloantigens by host cells. Eur J Immunol. 1986 May;16(5):569–574. doi: 10.1002/eji.1830160519. [DOI] [PubMed] [Google Scholar]
  28. Smith J. B., McIntosh G. H., Morris B. The traffic of cells through tissues: a study of peripheral lymph in sheep. J Anat. 1970 Jul;107(Pt 1):87–100. [PMC free article] [PubMed] [Google Scholar]
  29. Springer T., Galfré G., Secher D. S., Milstein C. Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur J Immunol. 1979 Apr;9(4):301–306. doi: 10.1002/eji.1830090410. [DOI] [PubMed] [Google Scholar]
  30. Steinman R. M., Gutchinov B., Witmer M. D., Nussenzweig M. C. Dendritic cells are the principal stimulators of the primary mixed leukocyte reaction in mice. J Exp Med. 1983 Feb 1;157(2):613–627. doi: 10.1084/jem.157.2.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Steinman R. M., Nogueira N., Witmer M. D., Tydings J. D., Mellman I. S. Lymphokine enhances the expression and synthesis of Ia antigens on cultured mouse peritoneal macrophages. J Exp Med. 1980 Nov 1;152(5):1248–1261. doi: 10.1084/jem.152.5.1248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Unkeless J. C. Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors. J Exp Med. 1979 Sep 19;150(3):580–596. doi: 10.1084/jem.150.3.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Van Voorhis W. C., Hair L. S., Steinman R. M., Kaplan G. Human dendritic cells. Enrichment and characterization from peripheral blood. J Exp Med. 1982 Apr 1;155(4):1172–1187. doi: 10.1084/jem.155.4.1172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Van Voorhis W. C., Valinsky J., Hoffman E., Luban J., Hair L. S., Steinman R. M. Relative efficacy of human monocytes and dendritic cells as accessory cells for T cell replication. J Exp Med. 1983 Jul 1;158(1):174–191. doi: 10.1084/jem.158.1.174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wahl S. M., Allen J. B., Dougherty S., Evequoz V., Pluznik D. H., Wilder R. L., Hand A. R., Wahl L. M. T lymphocyte-dependent evolution of bacterial cell wall-induced hepatic granulomas. J Immunol. 1986 Oct 1;137(7):2199–2209. [PubMed] [Google Scholar]
  36. Yelton D. E., Desaymard C., Scharff M. D. Use of monoclonal anti-mouse immunoglobulin to detect mouse antibodies. Hybridoma. 1981;1(1):5–11. doi: 10.1089/hyb.1.1981.1.5. [DOI] [PubMed] [Google Scholar]

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