It remains largely unclear how antigen-presenting cells (APCs) encounter effector or memory T cells efficiently in the periphery. Here we used a mouse contact hypersensitivity (CHS) model to show that upon epicutaneous antigen challenge, dendritic cells (DCs) formed clusters with effector T cells in dermal perivascular areas to promote in situ proliferation and activation of skin T cells in a manner dependent on antigen and the integrin LFA-1. We found that DCs accumulated in perivascular areas and that DC clustering was abrogated by depletion of macrophages. Treatment with interleukin 1α (IL-1α) induced production of the chemokine CXCL2 by dermal macrophages, and DC clustering was suppressed by blockade of either the receptor for IL-1 (IL-1R) or the receptor for CXCL2 (CXCR2). Our findings suggest that the dermal leukocyte cluster is an essential structure for elicitating acquired cutaneous immunity.

Topical CAL can exert its antipsoriatic effect on CAL-treated lesions and, concomitantly, distant lesions by attenuating the T17 cell accumulation in both CAL-treated lesions and draining lymph nodes.

Disclosure of potential conflict of interest: F. de Blay reports grants from Stallergenes-Greer and Chiesi and personal fees from ALK, Mundipharma, and Novartis, during the conduct of the study; and is a board member for Stallergenes-Greer, Novartis, ALK, Mundipharma, Medapharma, Boehringer, and Teva. M. Jutel reports lecture fees from ALK-Abello; lecture fees, advisory board, and clinical investigator fees from Allergopharma; lecture fees and clinical investigator fees from Stallergenes; advisory board and clinical investigator fees from Anergis; advisory board fees from Biomay and UCB; and clinical investigator fees from HAL, Astra-Zeneka, GSK, Novartis, Teva, Vectura, Tekada, Roche, Janssen, Medimmune, Allergy Therapeutics, Circassia, Leti, and Chiesi. L. Jacobsen and M. Worm received money for consulting fees and study preparation from Anergis SA. L. Jacobsen received money for study preparation from Anergis SA. M. Worm was paid for consultancy outside of this research by Anergis SA. A. Kettner, G. DellaCorte, V. Charlon, C. Reymond, and K. Simonsen are employees of Anergis SA and have stock options with this company. V. Charlon received travel/accommodations/meeting expenses from Anergis SA unrelated to this research. F. Spertini has stock/stock options with Anergis SA; received support for travel to meetings for the study or other purposes from Anergis SA; has patents (planned, pending, or issued) and received royalties from CHUV, Lausanne, CH; and is a funder of the company Anergis SA, which supported this study.

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