Costimulation

In the absence of costimulation, T cells that receive signaling through the TCR become anergic and unresponsive to new antigen stimulation. The anergic state in T cells results from activation of NFAT in the absence of AP-1. In this scenario, a specific set of genes is... 

Mechanism of peripheral immune tolerance characterized by a state of functional unresponsiveness induced in T cells by suboptimal or partial stimulation. Engagement of the antigen receptor in the absence of costimulation signaling induces anergy in T cells, which become unable to respond to new stimulations. 

Restivo VA Jr, Lombard LA. Gray GS. Nadler LM Cloning of B7-2 a CTLA-4 counter-receptor that 79 costimulates human T cell proliferation. Science 1993 262 909-911. 

Ohshima Y, Yang LP, Uchiyama T, Tanaka Y, Baum P, Sergerie M, Hermann P, Delespesse G 0X40 costimulation enhances interleukin-4 (IL-4) expression at priming and promotes the differentiation of naive human CD4i- T cells into high IL-4-producing effectors. Blood 1998 92 3338-3345. 

Singh B, Sharpe A, Bluestone JA B7/CD28 costimulation is essential for the homeostasis of the CD4-iCD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 2000 12 431-440. 

IL-10 inhibits CD28 and ICOS costimulations of T 127 cells via Src homology 2 domain-containing protein tyrosine phosphatase 1. J Allergy Chn Immunol 2007 120 76-83. 

The HIV-1 coreceptors CXCR4 and CCR5 bind to ligand members of a family of molecules known as chemokines, or chemotactic cytokines. While the hallmark function of these small proteins is the direction of leukocyte trafficking, they can also participate in cellular events such as activation and costimulation (Bajetto et al. 2(X)la). Members of the chemokine family can be classified as either homeostatic or inflammatory based on their temporal expression (Charo and Ransohoff 2006 Kim 2005). Although traditionally the CNS had been thought to be protected from immune acti-... 

Nanki T, Lipsky PE (2000) Cutting edge stromal cell-derived factor-1 is a costimulator for CD4-I-T cell activation. J Immunol 164 5010-5014... 

Sawai H, Park YW, Roberson J, Imai T, Goronzy JJ, Weyand CM. T cell costimulation by fractalkine-expressing synoviocytes in rheumatoid arthritis. Arthritis Rheum 2005 52(5) 1392-1401. 

Viola A, Schroeder S, Sakakibara Y, Lanzavecchia A. T lymphocyte costimulation mediated by reorganization of membrane microdomains. Science 1999 283(5402) 680-682. 

Gharaee-Kermani M, Denholm EM, Phan SH. Costimulation of fibroblast collagen and transforming growth factor betal gene expression by monocyte chemoattractant protein-1 via specific receptors. J Biol Chem 1996 271(30) 17779-17784. 

Reilly, T.P. et al., Role of immunomodulation by the selective costimulation modulator, abatacept, in initiated tumors, The Toxicologist, 90 50, 2006. 

Kremer, J.M. et al., Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept, Arthritis Rheum., 52, 2263, 2005. 

Abrams, J.R. et al., Blockade of T lymphocyte costimulation with Cytotoxic T Lymphocyte-associated Antigen 4-Immunoglobulin (CTL A4Ig) reverses the cellular pathology of psoriatic plaques, including the activation of keratinocytes, dendritic cells, and endothelial cells, J. Exp. Med., 192, 691, 2000. 

Forster, E. et al., Contribution of CD40-CD154-mediated costimulation to an alloresponse in vivo, Transplantation, 67, 1284, 1999. 

Pollard, K.M. et al., Costimulation requirements of induced murine systemic autoimmune disease, J. Immunol., 173, 5880, 2004. 

Tai X, Cowan M, Feigenbaum L, Singer A CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin-2. Nat Immunol 2005 6 152-162. 

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