Restoration of CD4+ Responses to Copathogens in HIV-Infected Individuals on Antiretroviral Therapy Is Dependent on T Cell Memory Phenotype.
J Immunol
; 195(5): 2273-2281, 2015 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-26195814
ABSTRACT
Antiretroviral therapy (ART) induces rapid suppression of viral replication and a progressive replenishment of CD4(+) T cells in HIV-infected individuals. However, the effect of ART on restoring pre-existing memory CD4(+) T cells specific for common copathogens is still unclear. To better understand the dynamics of Ag-specific CD4(+) T cells during ART, we assessed the frequency, functional capacity, and memory profile of CD4(+) T cells specific for Mycobacterium tuberculosis and CMV in 15 HIV-infected individuals before and 1 y after ART initiation. After ART initiation, the frequency of M. tuberculosis-specific CD4(+) T cells showed little change, whereas CMV-specific CD4(+) T cells were significantly lower (p = 0.003). There was no difference in the polyfunctional or memory profile of Ag-specific CD4(+) T cells before and after ART. The replenishment of Ag-specific CD4(+) T cells correlated with the memory differentiation profile of these cells prior to ART. Pathogen-specific CD4(+) T cells exhibiting a late differentiated profile (CD45RO(+)CD27(-)) had a lower capacity to replenish (p = 0.019; r = -0.5) compared with cells with an early differentiated profile (CD45RO(+)CD27(+); p = 0.04; r = 0.45). In conclusion, restoration of copathogen-specific memory CD4(+) T cells during treated HIV infection is related to their memory phenotype, in which early differentiated cells (such as most M. tuberculosis-specific cells) have a higher replenishment capacity compared with late differentiated cells (such as most CMV-specific cells). These data identify an important, hitherto unrecognized, factor that may limit restoration of copathogen immunity in HIV-infected individuals on ART.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Infecções por HIV
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Antirretrovirais
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Memória Imunológica
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article