Cytokine-induced human IFN-gamma-secreting effector-memory Th cells in chronic autoimmune inflammation.
Blood
; 113(9): 1948-56, 2009 Feb 26.
Article
em En
| MEDLINE
| ID: mdl-19104082
ABSTRACT
T-helper (Th) cells activated by cytokines in the absence of T-cell receptor ligation are suspected to participate in inflammatory processes by production of interferon-gamma (IFN-gamma). Still, the relevance of such a mechanism has not been addressed in humans. Here we demonstrate that a subset of human effector-memory Th cells expressing functional interleukin-12R (IL-12R), IL-18Ralpha, and CCR5 ex vivo can be induced to secrete IFN-gamma by cytokines signaling via the IL-2R common gamma-chain in combination with IL-12 and IL-18. Cytokine-driven IFN-gamma production depends on JAK3- and p38 mitogen-activated kinase signals and is sensitive to suppression by CD25(++) regulatory T cells. Contrary to IFN-gamma(+) Th cells induced upon antigen-specific stimulation, their cytokine-activated counterparts characteristically lack expression of costimulator 4-1BB (CD137). Strikingly, the majority of Th cells infiltrating inflamed joints of rheumatoid arthritis patients is equipped with receptors prerequisite for cytokine-induced IFN-gamma secretion. Among these cells, we detected a substantial fraction that secretes IFN-gamma directly ex vivo but lacks 4-1BB expression, indicating that cytokine-induced IFN-gamma(+) Th cells operate in autoimmune inflammation. Our data provide a rationale for how human effector-memory Thcells can participate in perpetuating inflammatory processes in autoimmunity even in the absence of T-cell receptor ligation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
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Citocinas
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Interferon gama
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Linfócitos T Auxiliares-Indutores
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Inflamação
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article