The therapeutic potential of positive and negative immune cell co-stimulation during inflammation.
Inflammatory cascades are initiated in response to alarm signals that may result from infection, malignant transformation or trauma. Immunity, however, must be controlled; otherwise damage may occur to otherwise healthy tissue within the same microenvironment. Similarly, peripheral tolerance mechanisms must ensure that autoreactive thymic or bone marrow emigrants do not respond upon encounter with the autoantigen. Organized lymphoid structures such as lymph nodes, spleen and Peyer's patches appear to regulate inflammation successfully, displaying controlled expansion and contraction. However, when immune cells flood into effector sites, the organization of T- and B-lymphocytes is lacking. What controls inflammatory cascades in lymph nodes but rarely in effector sites is not clear. We believe the difference lies in the Toll-like receptor ligand load, which is high in effector sites and drives uncontrolled inflammation. Similarly, we believe that initiation of autoimmune inflammation is initiated by the liberation of inflammatory signals due to infection or trauma. In this review, we highlight some of the molecules responsible for maintaining an activated T-cell phenotype, strategies to interrupt these therapeutically and the impact of ligating inhibitory receptors on antigen-presenting cells.
Gwyer
E
E
Kennedy Institute for Rheumatology, Imperial College London, 1, Aspenlea Road, London W6 8LH, UK.
Snelgrove
R
R
Hussell
T
T
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D005326:Fetal Proteins / Q000276:immunology; D006801:Humans; D007109:Immunity; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology; D051379:Mice; D018448:Models, Immunological; D011505:Protein-Tyrosine Kinases / Q000276:immunology
D015703:Antigens, CD; D005326:Fetal Proteins; D011505:Protein-Tyrosine Kinases; C475466:Kos1 protein, mouse; C098672:TNK1 protein, human; C042739:antigens, CD200