期刊
FRONTIERS IN IMMUNOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.02212
关键词
anti-DEC205; CTB; adjuvant; skin; memory; T cells; dendritic cells
类别
资金
- Instituto Mexicano del Seguro Social (IMSS) in Mexico [R-2015-785-023 FIS/IMSS/PROT/G151435]
- Consejo Nacional de Ciencia y Tecnologia (CONACyT) in Mexico [CB-2010-01157018, 180441]
- National Institute of Arthritis, Musculoskeletal and Skin Diseases of the US National Institutes of Health [R00 AR062595]
- National Cancer Institute of the US National Institutes of Health [R01 CA219994]
- Consejo Nacional de Ciencia y Tcenologia (CONACYT) in Mexico [275768]
- Coordinacion de Investigacion en Salud: Apoyo demovilidad internacional, programa de cooperacion internacional
- CONACyT [CVU 348201]
CD4(+) T cells are major players in the immune response against several diseases; including AIDS, leishmaniasis, tuberculosis, influenza and cancer. Their activation has been successfully achieved by administering antigen coupled with antibodies, against DC-specific receptors in combination with adjuvants. Unfortunately, most of the adjuvants used so far in experimental models are unsuitable for human use. Therefore, human DC-targeted vaccination awaits the description of potent, yet nontoxic adjuvants. The nontoxic cholera B subunit (CTB) can be safely used in humans and it has the potential to activate CD4(+) T cell responses. However, it remains unclear whether CTB can promote DC activation and can act as an adjuvant for DC-targeted antigens. Here, we evaluated the CTB's capacity to activate DCs and CD4(+) T cell responses, and to generate long-lasting protective immunity. Intradermal (i.d.) administration of CTB promoted late and prolonged activation and accumulation of skin and lymphoid-resident DCs. When CTB was co-administered with anti-DEC205-OVA, it promoted CD4(+) T cell expansion, differentiation, and infiltration to peripheral nonlymphoid tissues, i.e., the skin, lungs and intestine. Indeed, CTB promoted a polyfunctional CD4(+) T cell response, including the priming of Th1 and Th17 cells, as well as resident memory T (RM) cell differentiation in peripheral nonlymphoid tissues. It is worth noting that CTB together with a DC-targeted antigen promoted local and systemic protection against experimental melanoma and murine rotavirus. We conclude that CTB administered i.d. can be used as an adjuvant to DC-targeted antigens for the induction of broad CD4(+) T cell responses as well as for promoting long-lasting protective immunity.
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