Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have addressed the capacity of HIV-1 infection to alter the growth of primary CD4+ T cells, but at the clonal level. Single T cells were expanded in the presence of PHA, IL-2, and small numbers of accessory dendritic cells. We report two new findings. First, T cells from seropositive individuals, even those with AIDS and markedly reduced CD4+ counts, exhibit a normal cloning efficiency, and proliferative capacity. This result is in contrast to two prior reports of a low cloning efficiency in CD4+ T cells from HIV-1-infected patients. Second, when we added high doses of exogenous HIV-1 to T cell clones from control subjects, we observed infection but not cytotoxicity or loss of CD4+ cells, following addition of virus stocks at days 0, 3, and/or 7 of clonal growth. The same HIV-1 isolates markedly reduced CD4+ T cells in bulk mononuclear cultures. When tested at day 11, HIV-1 mRNA was expressed in some cells of exogenously infected clones by in situ hybridization; when tested at day 18, several clones could transactivate a TAT-sensitive cell line. These findings suggest that the loss of CD4+ T cells in infected individuals is not the inevitable result of the activation of latent infection, or spread of a productive infection, during clonal growth.
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PMID:Most CD4+ T cells from human immunodeficiency virus-1 infected patients can undergo prolonged clonal expansion. 257 7

Although JNK is a potential target for treating chronic inflammatory diseases, its role in T lymphocyte function remains controversial. To overcome some of the previous limitations in addressing this issue we have used the recently described transactivator of transcription-JNK-interacting protein (TAT-JIP) peptide, a specific inhibitor that was derived from the minimal JNK-binding region of the scaffold protein, JNK-interacting protein 1 (JIP-1), coupled to the short cell-permeable HIV TAT sequence. Pretreatment of purified human T lymphocytes with the TAT-JIP peptide inhibited the phosphorylation of endogenous jun activated by PHA-PMA. This was associated with a corresponding inhibition of lymphoproliferation, and of IL-2, IFN-gamma, lymphotoxin, and IL-10 cytokine production. Similar results were also found using mouse splenic T cells. Examination of the specificity of TAT-JIP revealed that although the peptide was more selective than the pharmacological inhibitor, SP600125, it also inhibited cyclin-dependent kinase 2, p70 ribosomal protein S6 kinase, and serum and glucocorticoid-regulated kinase activity. Nevertheless, these data demonstrate for the first time the ability of the TAT-JIP peptide to inhibit the JNK pathway and the phosphorylation of jun in intact cells, thereby preventing the activation of the transcription factor, AP-1, and the production of Th1 and Th2 cytokines. Thus JNK could potentially be a target for the development of drugs for the treatment of autoimmune inflammatory diseases.
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PMID:The effect of the JNK inhibitor, JIP peptide, on human T lymphocyte proliferation and cytokine production. 1898 Nov 52