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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, METHODS, RESULTS. Meshes: Adult, Aged, Anti-HIV Agents, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Extracellular Signal-Regulated MAP Kinases, Female, Flow Cytometry, HIV Infections, HIV-1, Humans, Lymphocyte Activation, Male, Middle Aged, Phenotype, Phosphorylation, Signal Transduction, Up-Regulation, Viral Load.
user
Is t-cell signalling in antiretroviral-treated , aviraemic HIV-1-positive individuals present in a raised state of basal activation that contributes to T-cell hyporesponsiveness? Context: Successful antiretroviral therapy (ART) suppresses plasma HIV-1 RNA below detection limits, reducing the chronic insult to the immune systems of infected individuals and supporting a degree of immunological recovery. However, the surface phenotypic profile of T cells in ART-treated patients does not resemble that of healthy, uninfected individuals, but rather shows upregulation of proteins associated with an exhausted immune system. We sought to address whether aviraemic HIV-1 infection, therefore, contributed to long-term alterations in intracellular signalling events within the T cells of infected individuals that contributed to the exhausted phenotype. A flow cytometric approach was employed to assess levels of phosphorylation within T-cell signalling proteins in ART-treated HIV-1-positive patients and HIV-negative individuals. The relative phosphorylation levels of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), p38, zeta-chain-associated protein kinase 70 (ZAP70), linker of activated T cells, SLP76, nuclear factor kappaB were measured within resting and stimulated CD4(+) and CD8(+) T cells from aviraemic HIV-1-positive and healthy individuals by intracellular staining and flow cytometric analysis. Basal levels of phospho-ZAP70, phospho-ERK and phospho-JNK were two-fold to three-fold higher in HIV-1-positive individuals compared with healthy controls, with phospho-p38 also showing a tendency to increase in HIV-1-positive individuals. Interestingly, in contrast to healthy controls, peripheral blood mononuclear cells from aviraemic, infected individuals were refractory to stimulation with IL-2 and CD3/CD28 showing no enhancement of phosphorylation.
assistant
CD4(+) and CD8(+) T cells from HIV-1-positive individuals are poorly responsive to direct stimulation through the T-cell receptor due to chronically raised basal activation levels of intracellular signalling molecules. Final Decision: yes