Epithelial adhesion molecules can inhibit HIV-1-specific CD8⺠T-cell functions.
Blood
; 117(19): 5112-22, 2011 May 12.
Article
em En
| MEDLINE
| ID: mdl-21403126
ABSTRACT
Under persistent antigenic stimulation, virus-specific CD8⺠T cells become increasingly dysfunctional and up-regulate several inhibitory molecules such as killer lectin-like receptor G1 (KLRG1). Here, we demonstrate that HIV-1 antigen-specific T cells from subjects with chronic-progressive HIV-1 infection have significantly elevated KLRG1 expression (P < .001); show abnormal distribution of E-cadherin, the natural ligand of KLRG1, in the intestinal mucosa; and have elevated levels of systemic soluble E-cadherin (sE-cadherin) that significantly correlate with HIV-1 viral load (R = 0.7, P = .004). We furthermore demonstrate that in the presence of sE-cadherin, KLRG1(hi) HIV-1-specific CD8⺠T cells are impaired in their ability to respond by cytokine secretion on antigenic stimulation (P = .002) and to inhibit viral replication (P = .03) in vitro. Thus, these data suggest a critical mechanism by which the disruption of the intestinal epithelium associated with HIV-1 leads to increased systemic levels of sE-cadherin, which inhibits the effector functions of KLRG1(hi)-expressing HIV-1-specific CD8⺠T cells systemically.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Caderinas
/
Infecções por HIV
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Transativadores
/
Linfócitos T CD8-Positivos
/
Lectinas Tipo C
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article