High proportion of PD-1-expressing CD4+ T cells in adipose tissue constitutes an immunomodulatory microenvironment that may support HIV persistence

5 years ago

High proportion of PD-1-expressing CD4+ T cells in adipose tissue constitutes an immunomodulatory microenvironment that may support HIV persistence

Benoit Favier, Stéphane Benoist, Olivier Lambotte, Jean-Jacques Lataillade, Elodie Busson, Thierry Lazure, Guillaume Pourcher, Michaela Müller-Trutwin, Bruno Vaslin, Abderaouf Damouche, Mélanie Van, Valérie Pourcher, Christine Bourgeois, Julien Adam

We and others have demonstrated that adipose tissue is a reservoir for HIV. Evaluation of the mechanisms responsible for viral persistence may lead to ways of reducing these reservoirs. Here, we evaluated the immune characteristics of adipose tissue in HIV-infected patients receiving antiretroviral therapy (ART) and in non-HIV-infected patients. We notably sought to determine whether adipose tissue's intrinsic properties and/or HIV induced alteration of the tissue environment may favour viral persistence. ART-controlled HIV infection was associated with a difference in the CD4/CD8 T-cell ratio and an elevated proportion of Treg cells in subcutaneous adipose tissue. No changes in Th1, Th2 and Th17 cell proportions or activation markers expression on T cell (Ki-67, HLA-DR) could be detected, and the percentage of CD69-expressing resident memory CD4+ T cells was not affected. Overall, our results indicate that adipose-tissue-resident CD4+ T cells are not extensively activated during HIV infection. PD-1 was expressed by a high proportion of tissue-resident memory CD4+ T cells in both HIV-infected patients and non-HIV-infected patients. Our findings suggest that adipose tissue's intrinsic immunomodulatory properties may limit immune activation and thus may strongly contribute to viral persistence. Adipose tissue CD4 T cells exhibit a tissue-specific profile defined by high expression of PD-1. The functional relevance of such high PD-1 expression on adipose CD4 T cells remains unclear but it may favor HIV persistence since PD1 expressing CD4 T cells has been described as a preferential HIV reservoir.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/eji.201747060