CD28, costimulation

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. 

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. 

Fang M, Sigal LJ. Direct CD28 costimulation is required for CD8+ T cell-mediated resistance to an acute viral disease in a natural host. J Immunol 2006 177 8027-8036. 

The compounds eugenin and saikochromone inhibited CD28-costimulated activation of human peripheral blood T cells (Chang et al. 2003). 

Lai JH, Ho LJ, Kwan CY, Chang DM, Lee TC. Plant alkaloid tetrandrine and its analog block CD28-costimulated activities of human peripheral blood T cells—Potential immunosuppressant in transplantation immunology. Transplantation 1999 68(9) ... 

Fontenot AP, Gharavi L, Bennett SR, et al. CD28 costimulation independence of target organ versus circulating memory antigen-specific CD4+ T cells. J Clin Invest 2003 112(5) 776 84. 

Kusmartsev, S.A., Li, Y., and Chen, S.H. (2000). Gr-1+ myeloid cells derived from tumor-bearing mice inhibit primary T cell activation induced through CD3/CD28 costimulation. J. Immunol. 165, 779-785. 

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. 

CD28 90 Most peripheral T cells. CD3+ thymocytes Costimulator for T-cell activation... 

Selective costimulation modulator, inhibits T cell activation by binding to CD80 and CD86, thereby blocking the interaction of CD28 Activation provides a co-stimulatory signal necessary for full activation of T cells... 

Other CD28 and B7 homologs continue to be identified and appear to play a role in costimulation. These molecules may provide additional targets for immunomodulation and suggest that it may be possible to fine-tune the immune response through pharmacologic intervention. 

Because the formation of a B7-CD28 complex between the APC and the T cell results In T-cell proliferation and the release of Inflammatory cytokines, whereas the B7-CTLA-4 Interaction Inhibits the T-cell responses, the design of a pharmacological agent that prevents costimulation would preferentially inhibit only reactive T cells and be effective in treatment of rheumatoid arthritis. Thus, the discovery of abatacept. 

Herold KC, Lu J, Ruhfson I, Vezys V, Taub D, Grusby MJ, Bluestone JA. Regulation of C-C chemokine production by murine T cells by CD28/B7 costimulation. J Immunol 1997 159 4150-4153. 

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