T cell activation

Structures ofMHC molecules have provided insights into the molecular mechanisms of T-cell activation... 

T-cell activating antigen although the aminopeptidase and immunological functions do not appear to interfere with each other. 

The antiinflammatory effects of statins likely result from their ability to inhibit the formation of mevalonic acid. Downstream products of this molecule include not only the end product, cholesterol, but also several isoprenoid intermediates that covalently modify ( pre-nylate ) certain key intracellular signaling molecules. Statin treatment reduces leukocyte adhesion, accumulation of macrophages, MMPs, tissue factor, and other proinflammatory mediators. By acting on the MHC class II transactivator (CIITA), statins also interfere with antigen presentation and subsequent T-cell activation. Statin treatment can also limit platelet activation in some assays as well. All these results support the concept that in addition to their favorable effect on the lipid profile, statins can also exert an array of antiinflammatory and immunomodulatory actions. 

Current evidence suggests that PPAR activation may limit inflammation and hence atherosclerosis. Both PPAR-a and PPAR-y can reduce T-cell activation, as shown by decreased production of EFN-y. PPAR-a agonists also rqness endothelial VCAM-1 expression and inhibit the inflammatory activation of vascular SMCs, while PPAR-y agonists repress endothelial chemokine expression and decrease macrophage MMP production. 

Cole et al. (1995) reported on knock-out mice with a germ line deletion of GR. They demonstrated that lack of GR leads to perinatal death, atelectasis of the lung, and lack of adrenalin synthesis. To circumvent perinatal lethality, Tranche et al. (1999) and Brewer et al. (2003) generated tissue-specific somatic deletions of GR. This allowed to characterize GR function in the CNS, the immune system, and the liver in more detail. In particular, these approaches revealed novel aspects of organ-specific glucocorticoid physiology such as anxiety-like behavior, growth control, and polyclonal T cell activation. 

Alefacept is a human recombinant integrin LFA3-IgG fusion protein that binds to the CD2 receptor thus blocking T-cell activation. 

NFAT was initially identified in activated T cells as a DNA binding activity required for IL-2 expression, a cytokine that plays a key role in T cell activation and survival. Subsequent studies revealed the involvement... 

The development of drugs that block Calcineuiin phosphatase activity has allowed successful prevention of graft rejection. Due to the key role that NFAT has in T-cell activation, these inhibitors behave as potent immunosuppressors. Nevertheless, the important roles that NFAT proteins have in other tissues suggest that exploring the use of similar drugs in other pathological contexts may be clinically and therapeutically relevant. 

Bacterial or viral proteins linking T-cell receptors and MHC molecules through simultaneous interaction with the constant domains of all MHC class II molecules and of T-cell receptor (3-chains. Hence, superantigens are polyclonal T-cell activators most likely involved in the development of autoimmune diseases. 

Tseng SY, Dustin ML (2002) T-cell activation a multidimensional signaling network. Curr. Opin. Cell Biol 14 575-580... 

The activation of DRF-3 through the TREF dependent pathway allows for chemokines such as RANTES to be produced. It also leads to the production of DFN-a and EFN-(3, which are involved in anti-viral immunity. The TREF pathway, activated by either TLR-3 or TLR-4, can also induce MHC class-II expression and costimulatory molecules, thus leading to T-cell activation. This provides an important link between innate and adaptive immunity. 

Pope, R.M., Wallis, R.S., Sailer, D., Buchanan. T.M., Pahlavani, M.A. (1991), T cell activation by mycobacterial antigens in inflammatory synovitis. Cell Immunol. 133,95-108. 

Quintana FJ, Gerber D, Kent SC, Cohen IR, Shai Y (2005) HIV-1 fusion peptide targets the TCR and inhibits antigen-specific T cell activation. J Chn Invest 115 2149-2158 Reeves JD, Gallo SA, Ahmad N, Miamidian JL, Harvey PE, Sharron M, Pohlmann S, Sfakianos JN, Derdeyn CA, Blumenthal R, Hunter E, Dorns RW (2002) Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics. Proc Natl Acad Sci USA 99 16249-16254... 

The roles of CD28 and CD40 ligand in T cell activation and tolerance. J Immunol 2000 164 4465-4470. 

Histopathology shows T-cell pathology and T-cell activation in acute reaction and in skin test... 

RCM-related T-cell activity may be assessed in vitro by lymphocyte transformation test [19, 24]. In addition, CD69 upregulation (lymphocyte activation test) was observed in patients with a positive lymphocyte transformation test [24, 39]. These tests appear to be a promising tool to identify drug-reactive T cells in the peripheral blood of patients with RCM-induced drug-hypersensitivity reactions. However, the sensitivity and specificity remain unknown and, therefore, these tests cannot be recommended for routine use yet, but further research on the specificity and sensitivity is indicated. 

In 1995, HlV-1 latency was first documented in HIV-1-infected patients when ex vivo T cell cultures were found to contain a subpopulation of cells that produced infectious virions when stimulated with T cell activators (Chun et al. 1995 Finzi et al. 1997). Latently infected T cells are rare, to the order of one in a million resting... 

Kieffer TL, Finucane MM, Nettles RE, Quinn TC, Broman KW, Ray SC, Persaud D, SUiciano RF (2004) Genotypic analysis of HIV-1 drug resistance at the limit of detection virus production without evolution in treated adults with undetectable HIV loads. J Infect Dis 189(8) 1452-1465 Kinoshita S, Su L, Amano M, Timmerman LA, Kaneshima H, Nolan GP (1997) The T cell activation factor NF-ATc positively regulates HIV-1 replication and gene expression in T cells. Immunity 6(3) 235-244... 

Lawrence DM, Durham LC, Schwartz L, Seth P, Marie D, Major EO (2004) Human immunodeficiency virus type 1 infection of human brain-derived progenitor cells. J Virol 78(14) 7319-7328 Li XY, Guo F, Zhang L, Kleiman L, Cen S (2007) APOBEC3G inhibits DNA strand transfer during HIV-1 reverse transcription. J Biol Chem 282(44) 32065-32074 Lin J, Cullen BR (2007) Analysis of the interaction of primate retroviruses with the human RNA interference machinery. J Virol 81(22) 12218-12226 Liu JO (2005) The yins of T cell activation. Sci STKE 2005(265) rel... 

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