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doi: 10.1097/QAD.0000000000000213
Basic Science

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

Tanaskovic, Saraa; Fernandez, Soniaa; Price, Patriciaa; French, Martyn A.a,b

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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 Lippincott Williams & Wilkins, Inc.


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