A role for dendritic cells in the priming of antigen-specific CD4+ and CD8+ T lymphocytes by immune-stimulating complexes in vivo

Beacock-Sharp, H., Donachie, A. M., Robson, N. C. and Mowat, A. M. (2003) A role for dendritic cells in the priming of antigen-specific CD4+ and CD8+ T lymphocytes by immune-stimulating complexes in vivo. International Immunology, 15(6), pp. 711-720. (doi: 10.1093/intimm/dxg067) (PMID:12750355)

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Abstract

Immune‐stimulating complexes (ISCOMS) are adjuvant vectors which are unusual in being able to prime both CD4+ and CD8+ T cells by parenteral and mucosal routes. However, their mode of action is unclear and to define better the cellular interactions involved we have studied the ability of ISCOMS containing ovalbumin (OVA) to prime TCR transgenic CD4+ or CD8+ T cells in vivo. Immunization with OVA ISCOMS caused activation and clonal expansion of CD4+ and CD8+ T cells in the T cell areas of the draining lymph nodes, followed by the migration of both CD4+ and CD8+ T cells into the B cell follicle. The T cells were primed to proliferate and secrete IFN‐γ after re‐stimulation in vitro with the appropriate OVA peptide and CD8+ T cell priming occurred in the absence of CD4+ T cells. Increasing the number of dendritic cells (DC) in vivo with flt3 ligand augmented the expansion and activation of the OVA‐specific T cells, particularly CD8+ T cells. These studies indicate DC play a central role in the priming of both CD4+ and CD8+ T cells in vivo, and suggest that an ability to target DC may allow ISCOMS to be powerful vaccine vectors for stimulating protective immunity.

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: Beacock-Sharp, H., Donachie, A. M., Robson, N. C., and Mowat, A. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:International Immunology
ISSN:0953-8178
ISSN (Online):1460-2377

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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