The role of antigen-presenting cells and interleukin-12 in the priming of antigen-specific CD4+ T cells by immune stimulating complexes

Robson, N. C., Beacock-Sharp, H., Donachie, A. M. and Mowat, A. M. (2003) The role of antigen-presenting cells and interleukin-12 in the priming of antigen-specific CD4+ T cells by immune stimulating complexes. Immunology, 110(1), pp. 95-104. (doi: 10.1046/j.1365-2567.2003.01705.x) (PMID:12941146)

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Abstract

Immune stimulating complexes (ISCOMs) containing the saponin adjuvant Quil A are vaccine adjuvants that promote a wide range of immune responses in vivo, including delayed-type hypersensitivity (DTH) and the secretion of both T helper 1 (Th1) and Th2 cytokines. However, the antigen-presenting cell (APC) responsible for the induction of these responses has not been characterized. Here we have investigated the role of dendritic cells (DC), macrophages (Mφ) and B cells in the priming of antigen-specific CD4+ T cells in vitro by ISCOMs containing ovalbumin (OVA). OVA ISCOMs pulsed bone marrow (BM)-derived DC but not BM Mφ, nor naïve B cells prime resting antigen-specific CD4+ T cells, and this response is greatly enhanced if DC are activated with lipopolysaccharide (LPS). Of the APC found in the spleen, only DC had the capacity to prime resting antigen specific CD4+ T cells following exposure to OVA ISCOMs in vitro, while Mφ and B cells were ineffective. DC, but not B cells purified from the draining lymph nodes of mice immunized with OVA ISCOMs also primed resting antigen-specific CD4+ T cells in vitro, suggesting that DC are also critical in vivo. Using DC and T cells from interleukin (IL)-12 p40−/− mice, we also identified a crucial role for IL-12 in the priming of optimal CD4+ T cell responses by OVA ISCOMs. We suggest that DC are the principal APC responsible for the priming of CD4+ T cells by ISCOMs in vivo and that directed targeting of these vectors to DC may enhance their efficancy as vaccine adjuvants.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Robson, Dr Neil and Mowat, Professor Allan and Donachie, Ms Anne Marie
Authors: Robson, N. C., Beacock-Sharp, H., Donachie, A. M., and Mowat, A. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunology
Publisher:John Wiley & Sons Ltd.
ISSN:0019-2805
ISSN (Online):1365-2567

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
229411Novel strategies in mucosal adjuvant construction based on the immuno-modulating properties of cholera toxin and ISCOMSAllan MowatEuropean Commission (EC)CT98-0505III -IMMUNOLOGY
266071MUCIMM Mucosal Immunization - Cluster ProjectAllan MowatEuropean Commission (EC)QLK2-CT-1999-00III -IMMUNOLOGY