Interleukin-7 signalling defects in naive CD4+ T cells of HIV patients with CD4+ T-cell deficiency onantiretroviral therapy are associated with T-cell activation and senescence
Objective: To examine the relationship of defects in interleukin (IL)-7-induced naive CD4+ T-cell homeostasis with residual immune activation and CD4+ T-cell senescence in HIV patients receiving antiretroviral therapy (ART) who exhibit persistent CD4+ T-cell deficiency. Design: IL-7 induced prolife...
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| Format: | Journal Article |
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Lippincott Williams and Wilkins
2014
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| Online Access: | http://hdl.handle.net/20.500.11937/40746 |
| _version_ | 1848755953721147392 |
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| author | Tanaskovic, S. Fernandez, S. Price, Patricia French, M. |
| author_facet | Tanaskovic, S. Fernandez, S. Price, Patricia French, M. |
| author_sort | Tanaskovic, S. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Objective: To examine the relationship of defects in interleukin (IL)-7-induced naive CD4+ T-cell homeostasis with residual immune activation and CD4+ T-cell senescence in HIV patients receiving antiretroviral therapy (ART) who exhibit persistent CD4+ T-cell deficiency. Design: IL-7 induced proliferation of, and IL-7 receptor signalling in, total and naive CD4+ T cells of HIV patients who had low (<350 cells/µl) or normal (>500 cells/µl) CD4+ T-cell counts on ART was examined and related to markers of CD4+ T-cell activation and senescence and innate immune activation. Methods: Total, naive (CD45RA+ CD27+) and CD31+ naive CD4+ T cells from aviremic HIV patients (n = 39) with nadir CD4+ T-cell counts less than 100 cells/µl, who had received ART for a median time of 7 (range 1–11) years, were assessed for CD127 expression, proliferation (Ki67), signal transducer and activator of transcription 5 phosphorylation (pSTAT5) and CD127 modulation following IL-7 stimulation. Changes were related to proportions of CD4+ T cells expressing HLA-DR or CD57 and plasma levels of sCD14, CXCL9 and CXCL10.Results: Patients with CD4+ T-cell deficiency exhibited lower expression of CD127 on total, naive and CD31+ naive CD4+ T cells. Downregulation of CD127 after culture with IL-7 correlated inversely with CD4+ T-cell counts and directly with Ki67 expression. Induction of pSTAT5 in CD4+ T-cell subsets was greater in patients with normal CD4+ T-cell counts. CD127 expression correlated inversely with proportions of CD4+CD57+ T cells, and pSTAT5 induction correlated inversely with CD4+ T-cell expression of HLA-DR and CD57. Conclusion: Defects of IL-7 signalling in HIV patients with persistent CD4+ T-cell deficiency receiving ART are associated with CD4+ T-cell activation and senescence. |
| first_indexed | 2025-11-14T09:04:30Z |
| format | Journal Article |
| id | curtin-20.500.11937-40746 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:04:30Z |
| publishDate | 2014 |
| publisher | Lippincott Williams and Wilkins |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-407462023-02-22T06:24:15Z Interleukin-7 signalling defects in naive CD4+ T cells of HIV patients with CD4+ T-cell deficiency onantiretroviral therapy are associated with T-cell activation and senescence Tanaskovic, S. Fernandez, S. Price, Patricia French, M. Signal transducer and activator of transcription 5 phosphorylation Senescence Interleukin-7 HIV Immune activation CD127 Objective: To examine the relationship of defects in interleukin (IL)-7-induced naive CD4+ T-cell homeostasis with residual immune activation and CD4+ T-cell senescence in HIV patients receiving antiretroviral therapy (ART) who exhibit persistent CD4+ T-cell deficiency. Design: IL-7 induced proliferation of, and IL-7 receptor signalling in, total and naive CD4+ T cells of HIV patients who had low (<350 cells/µl) or normal (>500 cells/µl) CD4+ T-cell counts on ART was examined and related to markers of CD4+ T-cell activation and senescence and innate immune activation. Methods: Total, naive (CD45RA+ CD27+) and CD31+ naive CD4+ T cells from aviremic HIV patients (n = 39) with nadir CD4+ T-cell counts less than 100 cells/µl, who had received ART for a median time of 7 (range 1–11) years, were assessed for CD127 expression, proliferation (Ki67), signal transducer and activator of transcription 5 phosphorylation (pSTAT5) and CD127 modulation following IL-7 stimulation. Changes were related to proportions of CD4+ T cells expressing HLA-DR or CD57 and plasma levels of sCD14, CXCL9 and CXCL10.Results: Patients with CD4+ T-cell deficiency exhibited lower expression of CD127 on total, naive and CD31+ naive CD4+ T cells. Downregulation of CD127 after culture with IL-7 correlated inversely with CD4+ T-cell counts and directly with Ki67 expression. Induction of pSTAT5 in CD4+ T-cell subsets was greater in patients with normal CD4+ T-cell counts. CD127 expression correlated inversely with proportions of CD4+CD57+ T cells, and pSTAT5 induction correlated inversely with CD4+ T-cell expression of HLA-DR and CD57. Conclusion: Defects of IL-7 signalling in HIV patients with persistent CD4+ T-cell deficiency receiving ART are associated with CD4+ T-cell activation and senescence. 2014 Journal Article http://hdl.handle.net/20.500.11937/40746 10.1097/QAD.0000000000000213 Lippincott Williams and Wilkins unknown |
| spellingShingle | Signal transducer and activator of transcription 5 phosphorylation Senescence Interleukin-7 HIV Immune activation CD127 Tanaskovic, S. Fernandez, S. Price, Patricia French, M. Interleukin-7 signalling defects in naive CD4+ T cells of HIV patients with CD4+ T-cell deficiency onantiretroviral therapy are associated with T-cell activation and senescence |
| title | Interleukin-7 signalling defects in naive CD4+ T cells of HIV patients with CD4+ T-cell deficiency onantiretroviral therapy are associated with T-cell activation and senescence |
| title_full | Interleukin-7 signalling defects in naive CD4+ T cells of HIV patients with CD4+ T-cell deficiency onantiretroviral therapy are associated with T-cell activation and senescence |
| title_fullStr | Interleukin-7 signalling defects in naive CD4+ T cells of HIV patients with CD4+ T-cell deficiency onantiretroviral therapy are associated with T-cell activation and senescence |
| title_full_unstemmed | Interleukin-7 signalling defects in naive CD4+ T cells of HIV patients with CD4+ T-cell deficiency onantiretroviral therapy are associated with T-cell activation and senescence |
| title_short | Interleukin-7 signalling defects in naive CD4+ T cells of HIV patients with CD4+ T-cell deficiency onantiretroviral therapy are associated with T-cell activation and senescence |
| title_sort | interleukin-7 signalling defects in naive cd4+ t cells of hiv patients with cd4+ t-cell deficiency onantiretroviral therapy are associated with t-cell activation and senescence |
| topic | Signal transducer and activator of transcription 5 phosphorylation Senescence Interleukin-7 HIV Immune activation CD127 |
| url | http://hdl.handle.net/20.500.11937/40746 |