Potential role for HIV-specific CD38-/HLA-DR+ CD8+ T cells in viral suppression and cytotoxicity in HIV controllers.
PLoS One
; 9(7): e101920, 2014.
Article
em En
| MEDLINE
| ID: mdl-25000587
ABSTRACT
BACKGROUND:
HIV controllers (HIC) are rare HIV-1-infected patients who exhibit spontaneous viral control. HIC have high frequency of CD38-/HLA-DR+ HIV-specific CD8+ T cells. Here we examined the role of this subset in HIC status. MATERIALS ANDMETHODS:
We compared CD38-/HLA-DR+ CD8+ T cells with the classical CD38+/HLA-DR+ activated phenotype in terms of 1) their activation status, reflected by CD69, CD25, CD71, CD40 and Ki67 expression, 2) functional parameters Bcl-2 expression, proliferative capacity, and IFN-γ and IL-2 production, and 3) cytotoxic activity. We also investigated how this particular profile is generated.RESULTS:
Compared to CD38+/HLA-DR+ cells, CD38-/HLA-DR+ cells exhibited lower expression of several activation markers, better survival capacity (Bcl-2 MFI, 367 [134-462] vs 638 [307-747], Pâ=â0.001), higher frequency of polyfunctional cells (15% [7%-33%] vs 21% [16%-43%], Pâ=â0.0003), greater proliferative capacity (0-fold [0-2] vs 3-fold [2]-[11], Pâ=â0.007), and higher cytotoxicity in vitro (7% [3%-11%] vs 13% [6%-22%], Pâ=â0.02). The CD38-/HLA-DR+ profile was preferentially generated in response to low viral antigen concentrations.CONCLUSIONS:
These data highlight the role of CD38-/HLA-DR+ HIV-specific CD8+ T cell cytotoxicity in HIC status and provide insights into the mechanism by which they are generated. Induction of this protective CD8+ subset may be important for vaccine strategies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Citotóxicos
/
Antígenos HLA-DR
/
Infecções por HIV
/
HIV-1
/
Linfócitos T CD8-Positivos
/
ADP-Ribosil Ciclase 1
Tipo de estudo:
Observational_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
França