Signal 3 and its role in autoimmunity 英文参考文献.docVIP

Arthritis Research Therapy Vol 6 No 1 Thomas Viewpoint Signal 3 and its role in autoimmunity Ranjeny Thomas Centre for Immunology and Cancer Research, Princess Alexandra Hospital, University of Queensland, Brisbane, Australia Corresponding author: Ranjeny Thomas (e-mail: rthomas@.au) Received: 6 Nov 2003 Accepted: 21 Nov 2003 Published: 19 Jan 2004 Arthritis Res Ther 2004, 6:26-27 (DOI 10.1186/ar1033) ? 2004 BioMed Central Ltd (Print ISSN 1478-6354; Online ISSN 1478-6362) What is the third signal? are consistent with the work of others, showing the impor- tant role of IL-12 in driving IFN-γ effector function by T cells [6]. Further upstream, IL-12 production by DCs has been shown to be driven by dual TLR (toll-like receptor) and CD40 signals [7]. In this regard, it is of interest that the minimum required signals for CD154 (CD40L) expres- sion by CD4+ T cells are CD80/86 and CD54, even in the absence of signal 1 [8]. Dendritic cells (DCs) are the professional antigen-present- ing cells (APCs) of the body, and as such play a key role in the signaling of T cells for effector responses to antigen. Various co-stimulatory and adhesive interactions between DCs and T cells are able to drive proliferative, proinflam- matory cytokine and cytotoxic effector functions of T cells [1]. The effector response made to antigen presented by DCs depends on the co-stimulatory signals delivered to T cells along with the antigen signal presented in the context of MHC molecules [2]. Lafferty’s concept of a second or co-stimulatory signal stands as a key model for our understanding of the generation of immunity, and also for our understanding of the basis for peripheral tolerance [3]. The signal 3 requirements for CD4+ T cells are less well defined. Indeed it is more difficult to define an effector function beyond cytokine production for CD4+ T cells that is equivalent t