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Expression of PD-1 and Tim-3 markers of T-cell exhaustion is associated with CD4 dynamics during the course of untreated and treated HIV infection

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Listed:
  • Norma Rallón
  • Marcial García
  • Javier García-Samaniego
  • Alfonso Cabello
  • Beatriz Álvarez
  • Clara Restrepo
  • Sara Nistal
  • Miguel Górgolas
  • José M Benito

Abstract

Introduction: T-cell exhaustion has been involved in the pathogenesis of HIV infection. We have longitudinally analyzed PD1 and Tim3 surrogate markers of T-cells exhaustion, in parallel with other markers of HIV progression, and its potential association with CD4 changes in treated and untreated infection. Patients and methods: 96 HIV patients, 49 of them followed in the absence of cART (cART-naïve group) and 47 after initiation of cART (cART group) were included and followed for a median of 43 [IQR: 31–60] months. PD1 and Tim3 expression, CD8 T-cells activation, recent thymic emigrants, activation/apoptosis and turnover of CD4 cells were assessed at baseline and during follow up. Univariate and multivariate associations with CD4 evolution were explored. Results: Parameters significantly associated with CD4 depletion in cART-naïve group were: baseline level (p = 0.02) and variation (p = 0.002) of PD1 and Tim3 co-expression on CD8, and variation of CD95 expression on CD4 (p = 0.007). Parameters significantly associated with CD4 restoration in cART group were: baseline level of CD38+HLADR- subset of CD8 (p = 0.01), variation of PD1 expression on CD8 (p = 0.036), variation of Tim3 expression on CD4 (p = 0.039) and variation of CD95 expression on CD4 (p = 0.035). Conclusions: Our results suggest that PD1 and Tim3 markers of exhaustion have a pivotal role in CD4 dynamics in HIV patients and its down-regulation would be a desirable effect of immunotherapies aimed to restore CD4 T-cell pool during progression of HIV infection.

Suggested Citation

  • Norma Rallón & Marcial García & Javier García-Samaniego & Alfonso Cabello & Beatriz Álvarez & Clara Restrepo & Sara Nistal & Miguel Górgolas & José M Benito, 2018. "Expression of PD-1 and Tim-3 markers of T-cell exhaustion is associated with CD4 dynamics during the course of untreated and treated HIV infection," PLOS ONE, Public Library of Science, vol. 13(3), pages 1-14, March.
  • Handle: RePEc:plo:pone00:0193829
    DOI: 10.1371/journal.pone.0193829
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    References listed on IDEAS

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    1. Cheryl L. Day & Daniel E. Kaufmann & Photini Kiepiela & Julia A. Brown & Eshia S. Moodley & Sharon Reddy & Elizabeth W. Mackey & Joseph D. Miller & Alasdair J. Leslie & Chantal DePierres & Zenele Mncu, 2006. "PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression," Nature, Nature, vol. 443(7109), pages 350-354, September.
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    1. Filipa Lynce & Candace Mainor & Renee N. Donahue & Xue Geng & Greg Jones & Ilana Schlam & Hongkun Wang & Nicole J. Toney & Caroline Jochems & Jeffrey Schlom & Jay Zeck & Christopher Gallagher & Rita N, 2024. "Adjuvant nivolumab, capecitabine or the combination in patients with residual triple-negative breast cancer: the OXEL randomized phase II study," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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