FAS/FAS-L dependent killing of activated human monocytes and macrophages by CD4+CD25- responder T cells, but not CD4+CD25+ regulatory T cells.
J Autoimmun
; 38(1): 29-38, 2012 Feb.
Article
en En
| MEDLINE
| ID: mdl-22197557
ABSTRACT
Conclusive resolution of an immune response is critical for the prevention of autoimmunity and chronic inflammation. We report that following co-culture with autologous CD4+CD25- responder T cells, human CD14+ monocytes and monocyte-derived macrophages become activated but also significantly more prone to apoptosis than monocytes/macrophages cultured alone. In contrast, in the presence of CD4+CD25+ regulatory T cells (Tregs), monocytes and macrophages survive whilst adopting an anti-inflammatory phenotype. The induction of monocyte death requires responder T cell activation and cell-contact between responder T cells and monocytes. We demonstrate a critical role for FAS/FAS-L ligation in responder T cell-induced monocyte killing since responder T cells, but not Tregs, upregulate FAS-ligand (FAS-L) mRNA, and induce FAS expression on monocytes. Furthermore, responder T cell-induced monocyte apoptosis is blocked by neutralising FAS/FAS-L interaction, and is not observed when monocytes from an autoimmune lymphoproliferative syndrome (ALPS) patient with complete FAS-deficiency are used as target cells. Finally, we show that responder T cell-induced killing of monocytes is impaired in patients with active rheumatoid arthritis (RA). Our data suggest that resolution of inflammation in the course of a healthy immune response is aided by the unperturbed killing of monocytes with inflammatory potential by responder T cells and the induction of longer-lived, Treg-induced, anti-inflammatory monocytes.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Monocitos
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Linfocitos T CD4-Positivos
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Linfocitos T Reguladores
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Receptor fas
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Proteína Ligando Fas
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Macrófagos
Límite:
Humans
Idioma:
En
Revista:
J Autoimmun
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Reino Unido