RGD Reference Report - Blockade of programmed death-1 in young (New Zealand black x New Zealand white)F1 mice promotes the activity of suppressive CD8+ T cells that protect from lupus-like disease. - Rat Genome Database

RGD Reference Report - Blockade of programmed death-1 in young (New Zealand black x New Zealand white)F1 mice promotes the activity of suppressive CD8+ T cells that protect from lupus-like disease. - Rat Genome Database

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Blockade of programmed death-1 in young (New Zealand black x New Zealand white)F1 mice promotes the activity of suppressive CD8+ T cells that protect from lupus-like disease.
Authors:	Wong, M La Cava, A Singh, RP Hahn, BH
Citation:	Wong M, etal., J Immunol. 2010 Dec 1;185(11):6563-71. doi: 10.4049/jimmunol.0903401. Epub 2010 Nov 1.
RGD ID:	7248678
Pubmed:	PMID:21041733 (View Abstract at PubMed)
DOI:	DOI:10.4049/jimmunol.0903401 (Journal Full-text)
The programmed death-1 (PD-1)/programmed death-1 ligand 1 (PD-L1) pathway regulates both stimulatory and inhibitory signals. In some conditions, PD-1/PD-L1 inhibits T and B cell activation, induces anergy, and reduces cytotoxicity in CD8(+) T cells. In other conditions, PD-l/PD-L1 has costimulatory effects on T cells. We recently showed that induction of suppressive CD8(+)Foxp3(+) T cells by immune tolerance of lupus-prone (New Zealand black x New Zealand white)F(1) (BWF(1)) mice with the anti-DNA Ig-based peptide pConsensus (pCons) is associated with significantly reduced PD-1 expression on those cells. In this study, we tested directly the role of PD-1 by administering in vivo neutralizing Ab to PD-1 to premorbid BWF(1) and healthy control mice. Anti-PD-1-treated mice were protected from the onset of lupus nephritis for 10 wk, with significantly improved survival. Although the numbers of T cells declined in aging control mice, they were maintained in anti-PD-1-treated mice, including CD8(+)Foxp3(+) T cells that suppressed syngeneic CD4(+)CD25(-) T cell proliferation and IFN-gamma production, reduced production of IgG and anti-dsDNA IgG, induced apoptosis in syngeneic B cells, and increased IL-2 and TGF-beta production. The administration of anti-PD-1 Ab to BWF(1) mice after induction of tolerance with pCons abrogated tolerance; mice developed autoantibodies and nephritis at the same time as control mice, being unable to induce CD8(+)Foxp3(+) T suppressor cells. These data suggest that tightly regulated PD-1 expression is essential for the maintenance of immune tolerance mediated by those CD8(+)Foxp3(+) T cells that suppress both T(h) cells and pathogenic B cells. PD-1 regulation could represent a target to preserve tolerance and prevent autoimmunity.

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
PDCD1	Human	lupus nephritis	onset	ISO	Pdcd1 (Mus musculus)		RGD
Pdcd1	Rat	lupus nephritis	onset	ISO	Pdcd1 (Mus musculus)		RGD
Pdcd1	Mouse	lupus nephritis	onset	IMP			RGD

Genes (Rattus norvegicus)


Pdcd1 (programmed cell death 1)

Genes (Mus musculus)


Pdcd1 (programmed cell death 1)

Genes (Homo sapiens)


PDCD1 (programmed cell death 1)