CTLA-4 (CD152) blockade does not cause a pro-inflammatory cytokine profile in regulatory T cells.
Clin Exp Rheumatol
; 29(2): 254-60, 2011.
Article
en En
| MEDLINE
| ID: mdl-21418778
OBJECTIVES: The activation of T cells is closely regulated. One cell intrinsic mechanism is based on the expression of inhibitory molecules; another is mediated by regulatory T (Treg) cells. The co-regulatory molecule CTLA-4 is constitutively expressed by Treg cells and up-regulated in effector-T-cells after activation. Recently, it was described that Treg cells can display an unstable phenotype and convert into pathogenic pro-inflammatory cytokine secreting cells. Here we have analysed the role of CTLA-4 in the regulation of cytokine production by T-helper (Th) cells with a special focus on Treg cells. METHODS: Proliferation of unstimulated CTLA-4 knock-out and wild-type cells as well as their activation status and the impact of CTLA-4 blockade on proliferation of Treg and effector T cells under stimulation were analysed by flow cytometry. Furthermore, the cytokine concentrations were analysed by a multiplex suspension assay. RESULTS: CTLA-4 knock-out T cells proliferated without stimulation and displayed an activated phenotype ex vivo. Proliferation of effector but also that of Treg cells was controlled by CTLA-4. The blockade of CTLA-4 led to an increased secretion of GM-CSF, IL-1ß, IL-2, and IFN-γ by Th cells. However, the blockade of CTLA-4 in Treg cells did not cause any conversion into pathogenic pro-inflammatory T cells, since the non-cytokine secreting phenotype remained unchanged. CONCLUSIONS: These results have major implications on therapies targeting the CTLA-4-system, e.g. by CTLA4-Ig or anti-CTLA-4-antibodies, as the blockade of CTLA-4 did not unlock the stability of Treg cells.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Autoinmunes
/
Antígenos CD
/
Linfocitos T Reguladores
/
Trastornos Linfoproliferativos
Límite:
Animals
Idioma:
En
Revista:
Clin Exp Rheumatol
Año:
2011
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Italia