Reduced T-cell activity

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. 

Although GPI anchor degradation is a possible mechanism for signal transduction in T-cell activation, it appears imlikely since PI-PLC treatment of lymphocytes does not stimulate, but rather, reduces T-cell activation [161]. Alternatively, the GPI-anchored protein may associate with other molecules that can transduce the signal into the cell. 

Basiliximab Chimeric IgGlK Sp2/0 a chain IL-2 receptor (CD25) Reduces T cell activation Prevent organ transplant rejection Simulect ... 

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. 

Cyclosporine and tacrolimus belong to a class of immunosuppressants called the calcineurin inhibitors. These agents are considered by many to be the cornerstone of medical immunosuppression. The calcineurin inhibitors work by complexingwith cytoplasmic proteins (cyclosporine with cyclophylin and tacrolimus with FK binding protein 12). These complexes then inhibit calcineurin phosphatase, which results in reduced IL-2 gene transcription. The final outcome is a decrease in IL-2 synthesis and a subsequent reduction in T cell activation.7 11 20 21... 

Cyclosporine reduces production of cytokines involved in T-cell activation and has direct effects on B cells, macrophages, bone, and cartilage cells. Its onset appears to be 1 to 3 months. Important toxicities at doses of 1 to 10 mg/kg/day include hypertension, hyperglycemia, nephrotoxicity, tremor, GI intolerance, hirsutism, and gingival hyperplasia. Cyclosporine should be reserved for patients refractory to or intolerant of other DMARDs. It should be avoided in patients with current or past malignancy, uncontrolled hypertension, renal dysfunction, immunodeficiency, low white blood cell or platelet counts, or elevated Ever function tests. 

Recently, PUFAs were shown to inhibit T cell activation by blocking key signal transduction events, specifically the activation of c-Jun NH2-terminal kinase (JNK) and NF-AT [62], Furthermore, the expression of CD25 (but not CD69) as well as the production of IL-2 and IL-13 (but not IFN-y, IL-4 and IL-10) was significantly reduced in PUFA-treated peripheral blood T cells. In a separate study, Li and colleagues reported... 

Szabo, G. et al., Reduced alloreactive T-cell activation after alcohol intake is due to impaired monocyte accessory cell function and correlates with elevated IL-10, IL-13, and decreased IFNgamma levels, Alcohol Clin. Exp. Res., 25, 1766, 2001. 

Iruretagoyena MI, Tobar JA, Gonzalez PA, Sepulveda SE, Figueroa CA, Burgos RA, Hancke JL, Kalergis AM. (2005) Andrographolide interferes with T-cell activation and reduces experimental autoimmune encephalomyelitis in the mouse. J Pharmacol Exp Ther 312 366-372. 

After reaching the lymph nodes, CD4+ cells are rapidly infected and replication of the virus continues. During the initial phase of infection, the virus is spread throughout the body via blood that contains many viral particles. The flu-like symptoms are first observed in about 70% of the patients 2-A weeks after HIV infection. At this stage, HIV titer is reduced due to the development of virus-specific CD8+ cells and due to humoral immune response, which generally causes a return to the normal numbers of CD4+ cells. As the HIV continues to replicate, a person may stay free of HIV-related symptoms for years. The high rate of mutation makes it impossible for the body to completely eliminate the HIV. Independent of mutation, certain subsets of HIV-recognizing killer T cells are not present or lack optimal function, and there is an inhibition of IFN secretion and cytotoxic T-cell activity due to impairment in the function of CD4+ cells. The HIV is also protected from immune surveillance when it hides within the chromosomes of the infected cells. 

Transgenic mice that overexpress Ab have been used to determine whether vaccines could be produced to reduce the concentration of the peptide in patients with AD. Experimental studies have shown that Ab peptide immunization reduces the cognitive impairments and the formation of plaques in rodent models of AD. This finding led to the development of vaccines for human use and while the phase 1 trials in the UK suggested that the vaccine was safe, more extensive studies in Europe led to the termination of the clinical trials because 5% of the patients develop meningioencephalitis. More studies are presently underway to induce an immune response against Ab without initiating T-cell activation which underlies the inflammatory process in the brain. 

Active infection with several viruses has been shown to reduce the ability of T cells to be activated (C3). Activated T cells (1 x 10s) normally produced 4-8 pg/ml per hr of GM-CSF after 20 hr of activation impaired T function resulted in a decrease to the 0.2 to 2.0 pg/ml per hour range of GM-CSF. Therefore, GM-CSF produced from T cells may be used as a marker for the suppression of T cells activation in viral infection (C14). 

T cell activation and can interfere with cytoskeletal components that prevent interleukin-2 sjmthesis and release. Cytotoxic edema caused by acute cerebral ischemia is associated with reduced diffusion, reflecting the failure of membrane sodium pumps. Altered electrolyte or fluid balance can precede the onset of encephalopathy. This can be shown by fluid-attenuated inversion recovery and diffusion-weighted MRI images (36). 

---