In situ recognition of autoantigen as an essential gatekeeper in autoimmune CD8+ T cell inflammation.
Proc Natl Acad Sci U S A
; 107(20): 9317-22, 2010 May 18.
Article
em En
| MEDLINE
| ID: mdl-20439719
ABSTRACT
A current paradigm states that non-antigen-specific inflammatory cues attract noncognate, bystander T cell specificities to sites of infection and autoimmune inflammation. Here we show that cues emanating from a tissue undergoing spontaneous autoimmune inflammation cannot recruit naive or activated bystander T cell specificities in the absence of local expression of cognate antigen. We monitored the recruitment of CD8(+) T cells specific for the prevalent diabetogenic epitope islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)(206-214) in gene-targeted nonobese diabetic (NOD) mice expressing a T cell "invisible" IGRP(206-214) sequence. These mice developed islet inflammation and diabetes with normal incidence and kinetics, but their inflammatory lesions could recruit neither naive (endogenous or exogenous) nor ex vivo-activated IGRP(206-214)-reactive CD8(+) T cells. Conversely, IGRP(206-214)-reactive, but not nonautoreactive CD8(+) T cells rapidly homed to and accumulated in the inflamed islets of wild-type NOD mice. Our results indicate that CD8(+) T cell recruitment to a site of autoimmune inflammation results from an active process that is strictly dependent on local display of cognate pMHC and suggest that CD8(+) T cells contained in extralymphoid autoimmune lesions are largely autoreactive.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autoantígenos
/
Proteínas
/
Autoimunidade
/
Ilhotas Pancreáticas
/
Glucose-6-Fosfatase
/
Linfócitos T CD8-Positivos
/
Diabetes Mellitus Tipo 1
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article