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Markers of Natural Killer Cell Exhaustion in HIV/HCV Coinfection and Their Dynamics After HCV Clearance Mediated by Direct-Acting Antivirals.
Osegueda, Ariel; Polo, Maria Laura; Baquero, Lucia; Urioste, Alejandra; Ghiglione, Yanina; Paz, Silvia; Poblete, Gabriela; Gonzalez Polo, Virginia; Turk, Gabriela; Quiroga, Maria Florencia; Laufer, Natalia.
Afiliação
  • Osegueda A; CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Buenos Aires, Argentina.
  • Polo ML; Universidad de Buenos Aires, Facultad de Medicina. Buenos Aires, Argentina.
  • Baquero L; CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Buenos Aires, Argentina.
  • Urioste A; Universidad de Buenos Aires, Facultad de Medicina. Buenos Aires, Argentina.
  • Ghiglione Y; CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Buenos Aires, Argentina.
  • Paz S; Universidad de Buenos Aires, Facultad de Medicina, Departamento de Microbiología, Parasitología e Inmunología, Buenos Aires, Argentina.
  • Poblete G; CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Buenos Aires, Argentina.
  • Gonzalez Polo V; Universidad de Buenos Aires, Facultad de Medicina. Buenos Aires, Argentina.
  • Turk G; CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Buenos Aires, Argentina.
  • Quiroga MF; Universidad de Buenos Aires, Facultad de Medicina. Buenos Aires, Argentina.
  • Laufer N; Hospital Francisco Javier Muñiz, Buenos Aires, Argentina.
Open Forum Infect Dis ; 10(12): ofad591, 2023 Dec.
Article em En | MEDLINE | ID: mdl-38107019
ABSTRACT

Background:

Liver fibrosis is a leading cause of morbimortality in people with HIV/hepatitis C virus (HCV). Natural killer (NK) cells are linked with amelioration of liver fibrosis; however, NK cells from individuals coinfected with HIV/HCV with cirrhosis display impaired functionality and high PD-1 expression. Here, we aimed to study PD-1, TIGIT, and Tim3 as potential exhaustion markers in NK cells from persons coinfected with HIV/HCV with mild and advanced liver fibrosis. We also evaluated the role of PD-1 expression on NK cells after HCV clearance by direct-acting antivirals (DAAs).

Methods:

Peripheral blood mononuclear cells were isolated from individuals coinfected with HIV/HCV (N = 54; METAVIR F0/F1, n = 27; F4, evaluated by transient elastography, n = 27). In 26 participants, samples were collected before, at the end of, and 12 months after successful DAA treatment. The frequency, immunophenotype (PD-1, TIGIT, and Tim3 expression), and degranulation capacity (CD107a assay) of NK cells were determined by flow cytometry.

Results:

Unlike PD-1, Tim3 and TIGIT were comparably expressed between persons with mild and advanced fibrosis. Degranulation capacity was diminished in NK/TIGIT+ cells in both fibrosis stages, while NK/PD-1+ cells showed a lower CD107a expression in cirrhotic cases. Twelve months after DAA treatment, those with advanced fibrosis showed an improved NK cell frequency and reduced NK/PD-1+ cell frequency but no changes in CD107a expression. In individuals with mild fibrosis, neither PD-1 nor NK cell frequency was modified, although the percentage of NK/CD107a+ cells was improved at 12 months posttreatment.

Conclusions:

Although DAA improved exhaustion and frequency of NK cells in cirrhotic cases, functionality was reverted only in mild liver fibrosis, remarking the importance of an early DAA treatment.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Open Forum Infect Dis Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Open Forum Infect Dis Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos