Subcutaneous cholera toxin exposure induces potent CD103⁺ dermal dendritic cell activation and migration

Apte, Simon H., Redmond, Andrew M., Groves, Penny L., Schussek, Sophie, Pattinson, David J., and Doolan, Denise L. (2013) Subcutaneous cholera toxin exposure induces potent CD103⁺ dermal dendritic cell activation and migration. European Journal of Immunology, 43 (10). pp. 2707-2717.

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Abstract

CD103⁺ dermal dendritic cells (dDCs) are a recently described DC subset of the skin shown to be the principal migratory DCs capable of efficiently cross-presenting antigens and activating CD8⁺ T cells. Harnessing their activity would promote vaccine efficacy, but it has been unclear how this can be achieved. We tested a panel of adjuvants for their ability to affect dDCs. In comparison to the other adjuvants tested, the capacity of cholera toxin (CT) to induce the migration of dDCs was unique. Within 24 h of CT injection, large numbers of highly activated dDCs (including CD103⁺ dDCs) migrated to the draining lymph nodes and cross-presented coinjected antigens, potently activating naïve CD8⁺ T cells. Peptide vaccines adjuvanted with CT induced T-cell responses uniquely characterized by dynamic cytokine responses including the production of IL-2, and such vaccines were protective in situations reliant on CD8⁺ T-cell responses, including liver-stage Plasmodium challenge, or tumor challenge. This study is the first to examine the effects of adjuvants on CD103⁺ dDCs and identifies CT as a prototypical adjuvant for the activation of CD103⁺ dDCs, opening the way to development of vaccines and adjuvants that specifically target dDCs and generate effective CD8⁺ T-cell responses.

Item ID: 41433
Item Type: Article (Refereed Research - C1)
Keywords: adjuvants; CD8+ T cells; cholera toxin; DCs; vaccines
ISSN: 1521-4141
Funders: National Health and Medical Research Council of Australia (NHMRC), Pfizer Australia Senior Research Fellowship (PASRF), Australian Centre for Vaccine Development (ACVD), University of Queensland (UQ)
Date Deposited: 13 Sep 2016 02:05
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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