2009
DOI: 10.1073/pnas.0813367106
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B7-H1 (PD-L1) on T cells is required for T-cell-mediated conditioning of dendritic cell maturation

Abstract: Studies have shown that T-cell-dendritic cell (DC) interaction is required for efficient DC maturation. However, the identities of the molecules that mediate the interaction in vivo are largely unknown. Here, we show that maturation of DCs as well as CD8 T-cell responses were impaired in B7-H1-deficient (B7-H1 ؊/؊ ) mice to influenza virus infection. Both defects were restored by transferring B7-H1-expressing naïve T cells into B7-H1 ؊/؊ mice. Similarly, transferring DCs from wild-type mice or from RAG1 ؊/؊ mi… Show more

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Cited by 67 publications
(50 citation statements)
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“…This may compensate for the lower PD-1 expression, ultimately yielding a balance in overall cellular activation. As CRC − mice had fewer T SLEC compared to WT, it is possible that early, optimal PD-1 expression may be required to coordinate an effective immune response, as has been previously reported (51), rather than acting as a cellular inhibitor as occurs during chronic stimulation. The decrease in effector CD8 T cells and/or function may be mediated through a number of mechanisms.…”
Section: Discussionmentioning
confidence: 78%
“…This may compensate for the lower PD-1 expression, ultimately yielding a balance in overall cellular activation. As CRC − mice had fewer T SLEC compared to WT, it is possible that early, optimal PD-1 expression may be required to coordinate an effective immune response, as has been previously reported (51), rather than acting as a cellular inhibitor as occurs during chronic stimulation. The decrease in effector CD8 T cells and/or function may be mediated through a number of mechanisms.…”
Section: Discussionmentioning
confidence: 78%
“…Our study adds that PD-1/PDL-1 regulation of CD8 T cell effector function is mediated locally by the epithelial cells of the lung, is regulated by IFNAR signaling, and can be therapeutically manipulated in the airways by intranasal administration of anti-PDL-1 blocking antibodies. Since PD-1 signaling has been shown to impact dendritic cell maturation, antigen presentation, and T cell priming and expansion (34,(42)(43)(44), it is important to differentiate the systemic role of PD-1/ PDL-1 during the generation of adaptive immune responses from the specific role at the mucosal site of infection during epithelial-T cell interaction cross talk.…”
Section: Discussionmentioning
confidence: 99%
“…Although this Fc-mediated effect is in fact required for the efficacy of some immunotherapeutic antibodies (14), it may in part be counterproductive in the case of this receptor-ligand pair. Both PD-1 and PD-L1 are expressed on the surface of antitumor cytotoxic T cells (15,16), and as such, antibodies targeting PD-1 and PD-L1 may paradoxically result in the undesirable depletion of the very lymphocytes they are intended to activate. Consistent with this hypothesis, treatment with anti-PD-1 antibodies of anti-PD-1 antibodies has been reported to correlate with lower circulating T-cell numbers in patients (17).…”
Section: Significancementioning
confidence: 99%