Anti-α4ß7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1-infected individuals.
Sci Transl Med
; 10(461)2018 10 03.
Article
em En
| MEDLINE
| ID: mdl-30282696
ABSTRACT
Gut homing CD4+ T cells expressing the integrin α4ß7 are early viral targets and contribute to HIV-1 pathogenesis, likely by seeding the gastrointestinal (GI) tract with HIV. Although simianized anti-α4ß7 monoclonal antibodies have shown promise in preventing or attenuating the disease course of simian immunodeficiency virus in nonhuman primate studies, the mechanisms of drug action remain elusive. We present a cohort of individuals with mild inflammatory bowel disease and concomitant HIV-1 infection receiving anti-α4ß7 treatment. By sampling the immune inductive and effector sites of the GI tract, we have discovered that anti-α4ß7 therapy led to a significant and unexpected attenuation of lymphoid aggregates, most notably in the terminal ileum. Given that lymphoid aggregates serve as important sanctuary sites for maintaining viral reservoirs, their attrition by anti-α4ß7 therapy has important implications for HIV-1 therapeutics and eradication efforts and defines a rational basis for the use of anti-α4ß7 therapy in HIV-1 infection.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Integrinas
/
Trato Gastrointestinal
/
Tecido Linfoide
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Sci Transl Med
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos