Asymptomatic HIV-infected individuals on antiretroviral therapy exhibit impaired lung CD4(+) T-cell responses to mycobacteria.
Am J Respir Crit Care Med
; 190(8): 938-47, 2014 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-25225948
ABSTRACT
RATIONALE HIV-infected persons on antiretroviral therapy (ART) remain at higher risk of pulmonary tuberculosis (TB) than HIV-uninfected individuals. This increased susceptibility may be caused by impairment of alveolar macrophage (AM) function and/or mycobacteria-specific alveolar CD4(+) T-cell responses observed in HIV-infected ART-naive adults. OBJECTIVES:
To determine whether ART was associated with improvement in both AM function, assessed by phagosomal proteolysis, and alveolar CD4(+) T-cell responses to Mycobacterium in HIV-infected individuals.METHODS:
Peripheral blood was drawn and bronchoalveolar lavage (BAL) performed on healthy, 35 HIV-uninfected, 25 HIV-infected ART-naive, and 50 HIV-infected ART-treated asymptomatic adults. Phagosomal proteolysis of AM was assessed with fluorogenic beads. Mycobacteria-specific CD4(+) T-cell responses were measured by intracellular cytokine staining. MEASUREMENTS AND MAINRESULTS:
HIV-infected adults on ART exhibited lower plasma HIV viral load and higher blood CD4(+) T-cell count than ART-naive adults. AM proteolysis and total mycobacteria-specific Th1 CD4(+) T-cell responses in individuals on ART for greater than or equal to 4 years were similar to HIV-uninfected control subjects but those on ART for less than 4 years had impaired responses. Total influenza-specific alveolar Th1 CD4(+) T-cell responses were intact in all individuals receiving ART. In contrast, BAL and blood mycobacteria-specific polyfunctional CD4(+) T-cell responses were impaired in adults on ART irrespective of duration.CONCLUSIONS:
AM and mycobacteria-specific alveolar CD4(+) T-cell responses in HIV-infected adults on ART for less than 4 years are impaired and may partly explain the high risk of TB in HIV-infected individuals on ART. Strategies to augment ART to improve lung immune cell function and reduce the high incidence of TB in HIV-infected adults who initiate ART should be investigated.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tuberculose Pulmonar
/
Linfócitos T CD4-Positivos
/
Infecções por HIV
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HIV-1
/
Macrófagos Alveolares
/
Fármacos Anti-HIV
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Mycobacterium tuberculosis
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Am J Respir Crit Care Med
Assunto da revista:
TERAPIA INTENSIVA
Ano de publicação:
2014
Tipo de documento:
Article