Exhaustion and senescence of CD4 and CD8 T cells that express co-stimulatory molecules CD27 and CD28 in subjects that acquired HIV by drug use or by sexual route

Leontina Bănică; Ovidiu Vlaicu; Raluca Jipa; Adrian Abagiu; Ionelia Nicolae; Emil Neaga; Dan Oţelea; Simona Paraschiv

doi:10.18683/germs.2021.1242

Exhaustion and senescence of CD4 and CD8 T cells that express co-stimulatory molecules CD27 and CD28 in subjects that acquired HIV by drug use or by sexual route

Germs. 2021 Mar 15;11(1):66-77. doi: 10.18683/germs.2021.1242. eCollection 2021 Mar.

Authors

Leontina Bănică¹, Ovidiu Vlaicu¹, Raluca Jipa², Adrian Abagiu², Ionelia Nicolae³, Emil Neaga¹, Dan Oţelea⁴, Simona Paraschiv⁵

Affiliations

¹ PhD, Molecular Diagnostics Laboratory, National Institute for Infectious Diseases "Prof. Dr. Matei Balş", No. 1 Dr. Calistrat Grozovici street, Bucharest 021105, Romania.
² MD, Clinical Department, National Institute for Infectious Diseases "Prof. Dr. Matei Balş", No. 1 Dr. Calistrat Grozovici street, Bucharest 021105, Romania.
³ MSc, Molecular Diagnostics Laboratory, National Institute for Infectious Diseases "Prof. Dr. Matei Balş", No. 1 Dr. Calistrat Grozovici street, Bucharest 021105, Romania.
⁴ MD, PhD, Molecular Diagnostics Laboratory, National Institute for Infectious Diseases "Prof. Dr. Matei Balş", No. 1 Dr. Calistrat Grozovici street, Bucharest 021105, Romania.
⁵ PhD, Molecular Diagnostics Laboratory, National Institute for Infectious Diseases "Prof. Dr. Matei Balş", No. 1 Dr. Calistrat Grozovici street, Bucharest 021105, Romania, Virology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

Abstract

Introduction: The human immunodeficiency virus (HIV) infection leads to immune activation, senescence and exhaustion of T cells. Co-stimulatory molecules play important roles in controlling these processes. The CD28 signaling triggers efficient T cell activation, while CD27 provides survival signals to CD28- T cells. Loss of these molecules was associated with senescent phenotype and resistance to checkpoint inhibitors.Romania has faced an HIV outbreak among people who inject drugs (PWID), most of them chronically infected with hepatitis C virus (HCV). HIV/HCV co-infection was associated with increased immune activation and rapid disease progression.

Methods: We evaluated by flow cytometry the expression of CD27, CD28, CD38, HLA-DR, CD57 and PD-1 on CD4 and CD8 T cells from 34 subjected infected with HIV (22 PWID and 12 people who acquired HIV by sexual route - PWHS) and 18 HIV-negative individuals (controls).

Results: We found that as compared to controls, HIV patients, regardless of infection route, have high percentages of intermediately differentiated (CD27+CD28-) and low percentages of less differentiated (CD27+CD28+) CD8 T cells. Significantly higher levels of CD8+CD27+CD28- T cells were found in PWHS than in PWID. A lower percentage of intermediately and highly differentiated (CD27-CD28-) CD8 T cells express CD57 in people living with HIV (PLWH) than in controls. Increased levels of less and intermediately differentiated CD4 and CD8 T cells expressing PD-1 were identified in PLWH, especially in PWID; these directly correlated with HIV viral load and T cell activation and negatively correlated with CD4 counts.

Conclusions: Our data show that induction of PD-1 on T cells expressing co-stimulatory molecules CD27 and/or CD28 might contribute to poor control of HIV infection and to immune activation.

Keywords: HIV/HCV co-infection; PWID; T cell exhaustion; co-stimulatory molecules.

GERMS.