| Inverse association of repressor growth factor independent-1 with CD8 T cell interleukin (IL)-7 receptor [alpha] expression and limited signal transducers and activators of transcription signaling in response to IL-7 among [gamma]-chain cytokines in HIV patients. | |
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MedLine Citation:
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PMID: 19579270 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: CD8 T lymphocytes from chronically infected HIV-positive patients degenerate into a preapoptotic state and exhibit impaired functionality. Particularly in viremic patients, this was associated with an increased proportion of interleukin-7 receptor-alpha low-expressing (IL-7Ralpha(low)) effector-like CD8 T cells. As cytokine signaling through signal transducers and activators of transcription (STAT) is essential for cellular function, we hypothesized that activation of this pathway may be impaired in these cells. OBJECTIVES: To evaluate cytokine-induced STAT activation in IL-7Ralpha(low) and IL-7Ralpha(high) CD8 T cells from chronically infected HIV-positive patients and investigate the potential molecular mechanism involved in the reduced IL-7Ralpha expression. METHODS: CD8 T cells from HIV-positive patients on and off antiretroviral therapy were assayed respectively for STAT activation, cytokine receptor, and transcription factor expression by flow cytometry and real-time PCR. RESULTS: IL-7 stimulation failed to activate STAT5 in a substantial proportion of patient CD8 T cells. This correlated with reduced IL-7Ralpha mRNA and surface protein expression. Interestingly, IL-7Ralpha(low) cells appeared to be fully capable of recruiting the STAT pathway in response to IL-2, IL-4, IL-10, and IL-15. mRNA expression suggested a potential role for growth factor independent (Gfi)-1 as an IL-7Ralpha transcriptional repressor, but not that of other transcriptional regulators studied, including Gfi-1B and GA-binding protein alpha. Programmed death-1 inhibitory receptor, though upregulated in CD8 T cells from HIV-positive patients, appeared unrelated to IL-7Ralpha expression and STAT signaling capacity. |
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Authors:
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Anita Benoit; Khaled Abdkader; Danylo Sirskyj; Abdulkarim Alhetheel; Nadia Sant; Francisco Diaz-Mitoma; Ashok Kumar; Marko Kryworuchko |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: AIDS (London, England) Volume: 23 ISSN: 1473-5571 ISO Abbreviation: AIDS Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-07-02 Completed Date: 2009-12-14 Revised Date: 2010-02-04 |
Medline Journal Info:
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Nlm Unique ID: 8710219 Medline TA: AIDS Country: England |
Other Details:
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Languages: eng Pagination: 1341-7 Citation Subset: IM; X |
Affiliation:
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Infectious Disease and Vaccine Research Centre, Children's Hospital of Eastern Ontario - Research Institute, Ottawa, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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CD8-Positive T-Lymphocytes
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immunology* Cytokines / genetics, immunology* HIV Infections / genetics, immunology* Humans Receptors, Cytokine / genetics, immunology* Signal Transduction / genetics, immunology* Transcription, Genetic |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Receptors, Cytokine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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