Characterization of CD4+ T-cell-dendritic cell interactions during secondary antigen exposure in tolerance and priming

Rush, C.M., Millington, O.R., Hutchison, S., Bryson, K., Brewer, J.M. and Garside, P. (2009) Characterization of CD4+ T-cell-dendritic cell interactions during secondary antigen exposure in tolerance and priming. Immunology, 128(4), pp. 463-471. (doi:10.1111/j.1365-2567.2009.03124.x)

Rush, C.M., Millington, O.R., Hutchison, S., Bryson, K., Brewer, J.M. and Garside, P. (2009) Characterization of CD4+ T-cell-dendritic cell interactions during secondary antigen exposure in tolerance and priming. Immunology, 128(4), pp. 463-471. (doi:10.1111/j.1365-2567.2009.03124.x)

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Publisher's URL: http://dx.doi.org/10.1111/j.1365-2567.2009.03124.x

Abstract

Despite the recent advances in our understanding of the dynamics of the cellular interactions associated with the induction of immune responses, comparatively little is known about the in vivo behaviour of antigen-experienced T cells upon secondary antigen exposure in either priming or tolerance. Such information would provide an insight into the functional mechanisms employed by memory T cells of distinct phenotypes and provide invaluable knowledge of how a specific tolerogenic or immunogenic state is maintained. Using real-time imaging to follow the in vivo motility of naïve, primed and tolerized CD4+ T cells and their interactions with dendritic cells (DCs), we demonstrate that each of these distinct functional phenotypes is associated with specific patterns of behaviour. We show that antigen-experienced CD4+ T cells, whether primed or tolerized, display inherently slower migration, making many short contacts with DCs in the absence of antigen. Following secondary exposure to antigen, primed T cells increase their intensity or area of interaction with DCs whereas contacts between DCs and tolerized T cells are reduced. Importantly, this was not associated with alterations in the contact time between DCs and T cells, suggesting that T cells that have previously encountered antigen are more effective at surveying DCs. Thus, our studies are the first to demonstrate that naïve, primed and tolerized T cells show distinct behaviours before and after secondary antigen-encounter, providing a novel mechanism for the increased immune surveillance associated with memory T cells. These findings have important consequences for many immunotherapeutics, which aim to manipulate secondary immune responses.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rush, Dr Catherine and Millington, Dr Owain and Garside, Professor Paul and Brewer, Professor James and Bryson, Dr Karen and Hutchison, Dr Sharon
Authors: Rush, C.M., Millington, O.R., Hutchison, S., Bryson, K., Brewer, J.M., and Garside, P.
Subjects:Q Science > QR Microbiology > QR180 Immunology
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunology
ISSN:0019-2805

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