Projects per year
Abstract
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 (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/ml, 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 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Original language | English |
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Pages (from-to) | 821-830 |
Journal | AIDS |
Volume | 28 |
Issue number | 6 |
DOIs | |
Publication status | Published - 27 Mar 2014 |
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Dive into the research topics of 'Interleukin-7 signalling defects in naive CD4+ T cells of HIV patients with CD4+ T-cell deficiency on antiretroviral therapy are associated with T-cell activation and senescence'. Together they form a unique fingerprint.Projects
- 1 Finished
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HIV & HCV Vaccines and Immunopathogenesis
French, M. (Investigator 01)
NHMRC National Health and Medical Research Council
31/12/08 → 31/12/13
Project: Research