Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 85, Issue 5, Pages 817-825Publisher
WILEY
DOI: 10.1189/jlb.0408246
Keywords
SEA; T cells; costimulation
Categories
Funding
- National Cancer Center, Korea [NCC-0810720-1, NCCF-08908301]
- Korean Research Foundation [KRF-2005-084-E00001]
- Arthritis Foundation
- National Institutes of Health grant [R001EY013325]
- Korea Health 21 RD [A050260]
- [MEST-2006-04212]
- [KOSEF-M1087006009-08N7006-00910]
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It has been reported that 4-1BB triggering in vivo selectively suppressed the recall response of staphylococcal enterotoxin A (SEA)-specific CD4(+) T cells, in which CD8(+) T-derived TGF-beta was involved. Here, we have examined an alternative mechanism for the 4-1BB-mediated CD4(+) T suppression, as the neutralization of TGF-beta is only effective in rescuing the SEA-specific recall response at high cellular concentrations. We show that this selective suppression of CD4(+) T cells by 4-1BB triggering in vivo is mediated mainly by induction of indoleamine 2,3-dioxygenase (IDO) in an IFN-gamma-dependent manner. SEA-specific CD4(+) T responses were suppressed partly by TGF-beta-expressing CD8(+) T cells, particularly CD11c(+)CD8(+) T cells, but strongly inhibited by dendritic cells (DCs) expressing IDO. IFN-gamma that increased IDO in DCs was produced primarily from CD11c(+) CD8(+) T cells, which were expanded selectively by 4-1BB stimulation. CD4(+), CD8(+), and plasmacytoid DCs exerted a similar suppressive activity toward the SEA-specific CD4(+) T cells. Neutralization of IFN-gamma or IDO activity in vivo largely reversed the 4-1BB-mediated CD4(+) T suppression. Collectively, these data indicate that 4-1BB-dependent suppression of SEA-specific CD4(+) T responses was mediated mainly by IFN-gamma-dependent IDO induction and partially by TGF-beta. J. Leukoc. Biol. 85: 817-825; 2009.
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