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Blockade of programmed death-1 in young (New Zealand Black x New Zealand White)F1
mice promotes the suppressive capacity of CD4+ regulatory T cells protecting from
lupus-like disease
#MMPMID23636058
Wong M
; La Cava A
; Hahn BH
J Immunol
2013[Jun]; 190
(11
): 5402-10
PMID23636058
show ga
Programmed death-1 (PD-1) usually acts as a negative signal for T cell
activation, and its expression on CD8(+)Foxp3(+) T cells is required for their
suppressive capacity. In this study, we show that PD-1 signaling is required for
the maintenance of functional regulatory CD4(+)CD25(+)Foxp3(+) regulatory T cells
(CD4(+) T(reg)) that can control autoimmunity in (New Zealand Black × New Zealand
White)F1 lupus mice. PD-1 signaling induced resistance to apoptosis and prolonged
the survival of CD4(+) T(reg). In vivo, the blockade of PD-1 with a neutralizing
Ab reduced PD-1 expression on CD4(+) T(reg) (PD1(lo)CD4(+) T(reg)). PD1(lo)CD4(+)
T(reg) had an increased ability to promote B cell apoptosis and to suppress
CD4(+) Th as compared with CD4(+) T(reg) with elevated PD-1 expression
(PD1(hi)CD4(+) T(reg)). When PD-1 expression on CD4(+) T(reg) was blocked in
vitro, PD1(lo)CD4(+) T(reg) suppressed B cell production of IgG and anti-dsDNA
Ab. Finally, in vitro studies showed that the suppressive capacity of CD4(+)
T(reg) depended on PD-1 expression and that a fine-tuning of the expression of
this molecule directly affected cell survival and immune suppression. These
results indicate that PD-1 expression has multiple effects on different immune
cells that directly contribute to a modulation of autoimmune responses.
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