AUTHOR=Rosado-Sánchez Isaac , Herrero-Fernández Inés , Genebat Miguel , Del Romero Jorge , Riera Melchor , Podzamczer Daniel , Olalla Julián , Vidal Francesc , Muñoz-Fernández Mª Angeles , Leal Manuel , Pacheco Yolanda M. 

TITLE=HIV-Infected Subjects With Poor CD4 T-Cell Recovery Despite Effective Therapy Express High Levels of OX40 and α4β7 on CD4 T-Cells Prior Therapy Initiation

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01673

DOI=10.3389/fimmu.2018.01673

ISSN=1664-3224

ABSTRACT=<sec id="ST1"><title>Background</title><p>HIV-infected subjects with suboptimal CD4 restoration despite suppressive combined antiretroviral treatment (cART) (immunodiscordant subjects) have been classically characterized after a variable period of time under cART. Recently, we have reported that an increased frequency of proliferating CD4 T-cells in these subjects is already present before the cART onset. The potential contribution of peripheral compensatory homeostatic proliferation (HP) is yet unknown. We aimed to analyze the expression of HP-related cellular markers on CD4 T-cells of immunodiscordant subjects before cART.</p></sec><sec id="ST2"><title>Methods</title><p>We analyzed the expression of OX40 and α4β7 on peripheral CD4 T-cells from immunodiscordant and control subjects (<italic>n</italic> = 21 each group) before cART initiation, and also on available follow-up samples (after 24 month of suppressive cART). Additionally, we tested the expression of these markers in an <italic>in vitro</italic> system for the study of human HP processes.</p></sec><sec id="ST3"><title>Results</title><p>Immunodiscordant subjects showed increased levels of OX40 and α4β7 on CD4 T-cells before cART initiation. While the cART tended to reduce these levels, immunodiscordant subjects still maintained comparatively higher levels of OX40 and α4β7 after 24 months under suppressive cART. These HP-related markers were upregulated <italic>in vitro</italic> during the human HP, especially during the fast HP.</p></sec><sec id="ST4"><title>Conclusion</title><p>Our results are compatible with exacerbated HP processes in immunodiscordant subjects, already before the cART onset.</p></sec>