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
Open Access
- 8 March 2018
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 13 (3), e0193829
- https://doi.org/10.1371/journal.pone.0193829
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-naYve 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-naYve 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.Keywords
Funding Information
- ISCIII (CP14/00198)
This publication has 32 references indexed in Scilit:
- Exhaustion of Activated CD8 T Cells Predicts Disease Progression in Primary HIV-1 InfectionPLoS Pathogens, 2016
- Programmed Death-1 Is a Marker for Abnormal Distribution of Naive/Memory T Cell Subsets in HIV-1 InfectionThe Journal of Immunology, 2013
- Pro- and anti-apoptotic CD95 signaling in T cellsCell Communication and Signaling, 2011
- Immune Exhaustion Occurs Concomitantly With Immune Activation and Decrease in Regulatory T Cells in Viremic Chronically HIV-1–Infected PatientsJAIDS Journal of Acquired Immune Deficiency Syndromes, 2010
- Role of the Fas/FasL Pathway in HIV or SIV DiseaseRetrovirology, 2009
- Programmed death (PD)-1 molecule and its ligand PD-L1 distribution among memory CD4 and CD8 T cell subsets in human immunodeficiency virus-1-infected individualsClinical and Experimental Immunology, 2009
- PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infectionThe Journal of Experimental Medicine, 2006
- Role of CD38 in HIV-1 infection: an epiphenomenon of T-cell activation or an active player in virus/host interactions?AIDS, 2000
- Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector FunctionThe Journal of Experimental Medicine, 1998
- Programmed cell death in peripheral lymphocytes from HIV-infected persons: increased susceptibility to apoptosis of CD4 and CD8 T cells correlates with lymphocyte activation and with disease progression.The Journal of Immunology, 1996