Autocrine production of beta-chemokines protects CMV-Specific CD4 T cells from HIV infection.
PLoS Pathog
; 5(10): e1000646, 2009 Oct.
Article
en En
| MEDLINE
| ID: mdl-19876388
ABSTRACT
Induction of a functional subset of HIV-specific CD4+ T cells that is resistant to HIV infection could enhance immune protection and decrease the rate of HIV disease progression. CMV-specific CD4+ T cells, which are less frequently infected than HIV-specific CD4+ T cells, are a model for such an effect. To determine the mechanism of this protection, we compared the functional response of HIV gag-specific and CMV pp65-specific CD4+ T cells in individuals co-infected with CMV and HIV. We found that CMV-specific CD4+ T cells rapidly up-regulated production of MIP-1alpha and MIP-1beta mRNA, resulting in a rapid increase in production of MIP-1alpha and MIP-1beta after cognate antigen stimulation. Production of beta-chemokines was associated with maturational phenotype and was rarely seen in HIV-specific CD4+ T cells. To test whether production of beta-chemokines by CD4+ T cells lowers their susceptibility to HIV infection, we measured cell-associated Gag DNA to assess the in vivo infection history of CMV-specific CD4+ T cells. We found that CMV-specific CD4+ T cells which produced MIP-1beta contained 10 times less Gag DNA than did those which failed to produce MIP-1beta. These data suggest that CD4+ T cells which produce MIP-1alpha and MIP-1beta bind these chemokines in an autocrine fashion which decreases the risk of in vivo HIV infection.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T CD4-Positivos
/
Infecciones por VIH
/
Quimiocinas CC
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
PLoS Pathog
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos