Expression and Function of NKG2D Is Impaired in CD8+ T Cells of Chronically HIV-1-Infected Patients Without ART.
J Acquir Immune Defic Syndr
; 70(4): 347-56, 2015 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-26509932
ABSTRACT
OBJECTIVES:
Increasing line of evidence indicates that the NKG2D-activating receptor plays a relevant role in the effector functions of cytotoxic lymphocytes. In this study, we investigated the expression and function of NKG2D in CD8⺠T cells from chronically HIV-1-infected patients with or without antiretroviral therapy (ART).METHODS:
We measured by flow cytometry the expression of NKG2D on CD8⺠T-cell subsets of ART-naive and ART patients as well as seronegative healthy subjects (HIV-neg). An intrapatient analysis before and after ART initiation was also performed. Results were correlated with viral load, CD4⺠T-cell counts, markers of immune activation (CD38, sCD14), and soluble NKG2D ligands (sMICA and sULBP2). The function of NKG2D on CD8⺠T cell cytotoxicity was tested by ex vivo degranulation assays.RESULTS:
We showed that NKG2D was downregulated on all CD8⺠T-cell subsets of ART-naive patients. The expression of NKG2D on CD8⺠T cells inversely correlated with viral load and CD38 expression but not with plasma levels of sMICA and sULBP2. Importantly, we found that NKG2D-mediated costimulation of CD8⺠T-cell lytic activity was strongly reduced in ART-naive patients if compared with HIV-neg and ART subjects. Finally, intrapatient analysis demonstrated that effective anti-HIV-1 therapy restores NKG2D expression and NKG2D-induced cytotoxicity by CD8⺠T cells.CONCLUSIONS:
These data underscore that NKG2D downregulation contributes to impaired CD8⺠T-cell responses in untreated HIV-1 infection and have implications for monitoring immune functions and response to treatments, and for the development of novel anti-HIV-1 strategies combining ART with drugs that stimulate NKG2D expression and function.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
Problema de salud:
2_enfermedades_transmissibles
Asunto principal:
Infecciones por VIH
/
Linfocitos T CD8-positivos
/
Perfilación de la Expresión Génica
/
Subfamilia K de Receptores Similares a Lectina de Células NK
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Acquir Immune Defic Syndr
Asunto de la revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Año:
2015
Tipo del documento:
Article
País de afiliación:
Italia