Distinct costimulation dependent and independent autoreactive T-cell clones in primary biliary cirrhosis.
Gastroenterology
; 125(5): 1379-87, 2003 Nov.
Article
em En
| MEDLINE
| ID: mdl-14598254
ABSTRACT
BACKGROUND & AIMS:
Previous work has suggested that CD4+ CD28- or costimulation-independent T cells are increased in autoimmune diseases. In this study, we compared frequency and qualitative characteristics of autoreactive costimulation-independent or CD4+ CD28- T cells in primary biliary cirrhosis (PBC) by taking advantage of the well-defined immunodominant autoepitope of the E2 component of pyruvate dehydrogenase (PDC-E2).METHODS:
We determined the frequency of costimulation-independent autoreactive T cells that respond to PDC-E2 163-176 and the frequency of CD4+ CD28- T cells. Finally, we determined the role of biliary epithelial cells (BEC) as both an antigen-presenting cell or, alternatively, as a target cell for T-cell-mediated cytotoxicity.RESULTS:
The precursor frequency of costimulation-independent CD4+ T cells that respond to PDC-E2 163-176 and the frequency of CD4+ CD28- T cells were dramatically elevated in PBC. Furthermore, 2 types of T-cell clones that respond to PDC-E2 163-176 emerged from this study. One type was costimulation dependent and the other costimulation independent. Both types of clones lyse BEC in a similar effector target (E/T) ratio distribution. However, BEC did not help the proliferation of any T-cell clones. Furthermore, costimulation-independent T-cell clones do not become anergic by BEC.CONCLUSIONS:
In PBC, costimulation-independent autoreactive T cells, which do not become anergic, increase and maintain the autoimmune response. In controls, although autoantigens are expressed on BEC and autoantigen-reactive T cells exist around BEC, autoantigen-reactive T cells are costimulation dependent and will become anergic and maintain peripheral tolerance.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Autoimunidade
/
Células Clonais
/
Cirrose Hepática Biliar
Tipo de estudo:
Qualitative_research
Limite:
Humans
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article