Human circulating CD4+CD25highFoxp3+ regulatory T cells kill autologous CD8+ but not CD4+ responder cells by Fas-mediated apoptosis.
J Immunol
; 182(3): 1469-80, 2009 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-19155494
ABSTRACT
Mechanisms utilized by human regulatory T cells (Treg) for elimination of effector cells may vary. We investigated the possibility that the mechanism of Treg suppression depends on Fas/FasL-mediated apoptosis of responder cells (RC). CD4(+)CD25(high)Foxp3(+) Treg and autologous CD4(+)CD25(-) and CD8(+)CD25(-) subsets of RC were isolated from blood of 25 cancer patients and 15 normal controls and cocultured in the presence of OKT3 and IL-2 (150 or 1000 IU/ml). Suppression of RC proliferation was measured in CFSE assays. RC and Treg apoptosis was monitored by 7-aminoactinomycin D staining in flow-based cytotoxicity assays. Treg from all subjects expressed CD95(+), but only Treg from cancer patients expressed CD95L. These Treg, when activated via TCR plus IL-2, up-regulated CD95 and CD95L expression (p < 0.001) and suppressed CD8(+) RC proliferation (p < 0.001) by inducing Fas-mediated apoptosis. However, Treg cocultured with CD4(+) RC suppressed proliferation independently of Fas/FasL. In cocultures, Treg were found to be resistant to apoptosis in the presence of 1000 IU/ml IL-2, but at lower IL-2 concentrations (150 IU/ml) they became susceptible to RC-induced death. Thus, Treg and RC can reciprocally regulate Treg survival, depending on IL-2 concentrations present in cocultures. This divergent IL-2-dependent resistance or sensitivity of Treg and RC to apoptosis is amplified in patients with cancer.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T CD4-Positivos
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Apoptosis
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Linfocitos T Reguladores
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Linfocitos T CD8-positivos
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Receptor fas
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Citotoxicidad Inmunológica
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Factores de Transcripción Forkhead
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Subunidad alfa del Receptor de Interleucina-2
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Inhibidores de Crecimiento
Límite:
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
Revista:
J Immunol
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos