Disruption of the JakSTAT cytokine signaling pathway in T cells from HIV-infected patients

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Title: Disruption of the JakSTAT cytokine signaling pathway in T cells from HIV-infected patients
Authors: Abd kader, Khaled
Date: 2007
Abstract: HIV infection leads to a profound T cell dysfunction well before the clinical onset of AIDS. This study investigated whether alterations in the Janus kinase (Jak)/signal transducer and activator of transcription (STAT) pathway in CD4+ and CD8+ T cells from HIV-infected patients induced by the growth promoting cytokines IL-2, IL-4, IL-7, IL-10, and IL-15 may be involved. IL-2 and IL-15 induced STAT5 phosphorylation (P-STAT5) in CD4+ T cells but there was a clear separation of cells into P-STAT5- and P-STAT5+ populations to similar proportions in HIV- and HIV+ patients. In response to IL-7, the proportion of P-STAT5- cells was significantly higher in HIV+ patients compared to HIV- controls. The IL-7 dependent P-STAT5- CD4+ T cells appeared to correlate with a lack of IL-7Ralpha chain expression. However, the P-STATS- cells observed did not correlate significantly with other cytokine receptor components. Cytokine-induced P-STAT5 in the CD8+ T cells from HIV+ patients was clearly detected. However, IL-2 and IL-15 stimulation revealed a P-STATS- CD8+ T cell population, which was not detected in HIV- subjects. P-STATS- CD8+ T cells were observed in all HIV+ patients studied in response to IL-2 and IL-15, irrespective of HAART. Defects in the IL-2 and IL-15 mediated signaling pathways appeared to exist downstream of cytokine receptor expression. In response to IL-7, P-STATS- cells were observed in both HIV+ and HIV- patients. However, their proportion was higher in HIV+ patients and returned towards that of HIV- controls under HAART and correlated inversely with IL-7Ralpha chain expression. The presence of P-STATS- CD8+ T cells did not correlate with the expression of other cytokine receptor chains. The P-STAT5- T cells observed in response to these cytokines may represent cells at distinct differentiation stages and functional capacities that arise in response to chronic HIV infection and may contribute to the eventual insufficiency of the cell mediated immune response.
URL: http://hdl.handle.net/10393/27566
http://dx.doi.org/10.20381/ruor-12145
CollectionTh├Ęses, 1910 - 2010 // Theses, 1910 - 2010
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