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 5 June 2000.

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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
c/o Ms. Sue Adams, Dept. of Immunology-178, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.713-745-1633713-792-8380

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 system that enables multiple functions of DCs to be assessedin vivo. Immunohistochemistry of skin sections revealed no differencesin terms of numbers and morphology of dendritic epidermal Langerhanscells (LCs) in unsensitized CD40 ligand –/– miceas compared with wild-type C57BL/6 mice. However, after contactsensitization of CD40 ligand –/– mice, LCs failedto migrate out of the skin and substantially fewer DCs accumulatedin draining lymph nodes (DLNs). Furthermore, very few antigen-bearingDCs could be detected in the paracortical region of lymph nodesdraining sensitized skin. This defect in DC migration afterhapten sensitization was associated with defective CHS responsesand decreased cutaneous tumor necrosis factor (TNF)- ${alpha}$ productionand was corrected by injecting recombinant TNF- ${alpha}$ or an agonisticanti-CD40 monoclonal antibody. Thus, CD40–CD40 ligandinteractions in vivo regulate the migration of antigen-bearingDCs from the skin to DLNs via TNF- ${alpha}$ production and play a vitalrole in the initiation of acquired T cell–mediated immunity.

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

A.M. Moodycliffe and V. Shreedhar contributed equally to thiswork.

Abbreviations used in this paper: CHS, contact hypersensitivity;DCs, dendritic cells; DETCs, dendritic epidermal T cells; DLNs,draining lymph nodes; LCs, dendritic epidermal Langerhans cells.

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