CD40-CD40 Ligand Interactions In Vivo Regulate Migration of Antigen-bearing Dendritic Cells from the Skin to Draining Lymph Nodes

doi:10.1084/jem.191.11.2011

Published online 6 June 1999.

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© The Rockefeller University Press, 0022-1007/2000/6/2011/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 11, June 5, 2000 2011-2020

Original Article

CD40–CD40 Ligand Interactions In Vivo Regulate Migration of Antigen-bearing Dendritic Cells from the Skin to Draining Lymph Nodes

Angus M. Moodycliffe^a, Vijay Shreedhar^c, Stephen E. Ullrich^a, Jeffrey Walterscheid^a, Corazon Bucana^b, Margaret L. Kripke^a, and Leopoldo Flores-Romo^a
^a Department of Immunology-178, M.D. Anderson Cancer Center, Houston, Texas 77030
^b Department of Cancer Biology-173, M.D. Anderson Cancer Center, Houston, Texas 77030
^c GI Research Laboratory, Harvard Medical School, Boston, Massachusetts 02115

Correspondence to: Leopoldo Flores-Romo, c/o Ms. Sue Adams, Dept. of Immunology-178, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Tel:713-792-8380 Fax:713-745-1633 E-mail:sadams{at}notes.mdacc.tmc.edu.

Whereas CD40–CD40 ligand interactions are important forvarious dendritic cell (DC) functions in vitro, their in vivorelevance is unknown. We analyzed the DC status of CD40 ligand-/- mice using a contact hypersensitivity (CHS) model systemthat enables multiple functions of DCs to be assessed in vivo.Immunohistochemistry of skin sections revealed no differencesin terms of numbers and morphology of dendritic epidermal Langerhanscells (LCs) in unsensitized CD40 ligand -/- mice as comparedwith wild-type C57BL/6 mice. However, after contact sensitizationof CD40 ligand -/- mice, LCs failed to migrate out of the skinand substantially fewer DCs accumulated in draining lymph nodes(DLNs). Furthermore, very few antigen-bearing DCs could be detectedin the paracortical region of lymph nodes draining sensitizedskin. This defect in DC migration after hapten sensitizationwas associated with defective CHS responses and decreased cutaneoustumor necrosis factor (TNF)- ${alpha}$ production and was corrected byinjecting recombinant TNF- ${alpha}$ or an agonistic anti-CD40 monoclonalantibody. Thus, CD40–CD40 ligand interactions in vivoregulate the migration of antigen-bearing DCs from the skinto DLNs via TNF- ${alpha}$ production and play a vital role in the initiationof acquired T cell–mediated immunity.

Key Words: Langerhans cells, epidermis, TNF- ${alpha}$ , contact hypersensitivity,acquired immunity

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