Emerging mechanisms of immune regulation the extended B7 family and regulatory T cells.docVIP

Arthritis Research Therapy Vol 6 No 5 Loke and Allison Review Emerging mechanisms of immune regulation: the extended B7 family and regulatory T cells P’ng Loke and James P Allison Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA Corresponding author: James P Allison, jallison@ Received: 12 May 2004 Revisions requested: 29 Jun 2004 Revisions received: 13 Jul 2004 Accepted: 19 Jul 2004 Published: 6 Aug 2004 Arthritis Res Ther 2004, 6:208-214 (DOI 10.1186/ar1225) ? 2004 BioMed Central Ltd Abstract Whereas B7-1/B7-2 and CD28/cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) serve as the main switches regulating the clonal composition of activated naive T cells, other B7 family members fine-tune the expansion and properties of activated T cells. Inducible costimulatory molecule (ICOS)–B7h promotes T-dependent antibody isotype switching and expansion of effector cells. Effector T cells trafficking into inflamed tissues interact with antigen-presenting cells there and are regulated by PD-1 and its ligands. B7-H3 and B7x could control the interaction between effector T cells and the peripheral tissues. The different varieties of regulatory T cells could regulate both naive T cell activation and effector function through costimulatory receptor/ligands. Keywords: antitumor immunity, autoimmunity, costimulation, inflammation, regulatory T cells Introduction In the past decade we have come a long way in terms of levels of complexity from the original two-signal hypothesis [1], which proposed that T cell activation required stimulation both via the T cell receptor (TCR) (signal 1) and through additional costimulatory molecules (signal 2). Instead of a simple binary on/off switch for the initiation of a T cell response, we now understand that costimulation orchestrates the clonal composition and features of the The discovery a