title: PD-L1 Blockade Differentially Impacts Regulatory T Cells from HIV-Infected Individuals Depending on Plasma Viremia.
abstract: Blocking the PD-1/PD-L1 pathway has emerged as a potential therapy to restore impaired immune responses in human immunodeficiency virus (HIV)-infected individuals. Most reports have studied the impact of the PD-L1 blockade on effector cells and neglected possible effects on regulatory T cells (Treg cells), which play an essential role in balancing immunopathology and antiviral effector responses. The aim of this study was to define the consequences of ex vivo PD-L1 blockade on Treg cells from HIV-infected individuals. We observed that HIV infection led to an increase in PD-1+ and PD-L1+ Treg cells. This upregulation correlated with disease progression and decreased under antiretroviral treatment. Treg cells from viremic individuals had a particularly high PD-1 expression and impaired proliferative capacity in comparison with Treg cells from individuals under antiretroviral treatment. PD-L1 blockade restored the proliferative capacity of Treg cells from viremic individuals but had no effect on its suppressive capacity. Moreover, it increased the viral production in cell cultures from viremic individuals. This increase in viral production correlated with an increase in Treg cell percentage and a reduction in the CD4/Treg and CD8/Treg cell ratios. In contrast to the effect of the PD-L1 blockade on Treg cells from viremic individuals, we did not observe a significant effect on the proliferative capacity of Treg cells from individuals in whom viremia was controlled (either spontaneously or by antiretroviral treatment). However, PD-L1 blockade resulted in an increased proliferative capacity of HIV-specific-CD8 T cells in all subjects. Taken together, our findings suggest that manipulating PD-L1 in vivo can be expected to influence the net gain of effector function depending on the subject's plasma viremia.
authors.affiliation: Infection Biology Laboratory, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Peligero
authors.affiliation: Infection Biology Laboratory, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Argilaguet
authors.affiliation: Infectious Diseases Unit, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Güerri-Fernandez
authors.affiliation: Infectious Diseases Unit, Hospital Clínic, Barcelona, Spain.
authors.forename: Berta
authors.initials: B
authors.lastname: Torres
authors.affiliation: Infectious Diseases Unit, Hospital Clínic, Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ligero
authors.affiliation: Infectious Diseases Unit, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Colomer
authors.affiliation: Retrovirology and Viral Immunopathology Laboratory, AIDS Research Group, IDIBAPS, Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Plana
authors.affiliation: Infectious Diseases Unit, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Hernando
authors.initials: H
authors.lastname: Knobel
authors.affiliation: Infectious Diseases Unit, Hospital Clínic, Barcelona, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: García
authors.affiliation: Infection Biology Laboratory, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyerhans
mesh_terms: D060890:B7-H1 Antigen / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000821:virology; D014766:Viremia / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor