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Publication : Identification of CD3+CD4-CD8- T cells as potential regulatory cells in an experimental murine model of graft-versus-host skin disease (GVHD).

First Author  Miyagawa F Year  2013
Journal  J Invest Dermatol Volume  133
Issue  11 Pages  2538-2545
PubMed ID  23648548 Mgi Jnum  J:202379
Mgi Id  MGI:5518964 Doi  10.1038/jid.2013.212
Citation  Miyagawa F, et al. (2013) Identification of CD3(+)CD4(-)CD8(-) T Cells as Potential Regulatory Cells in an Experimental Murine Model of Graft-Versus-Host Skin Disease (GVHD). J Invest Dermatol 133(11):2538-45
abstractText  We have developed K14-mOVA transgenic (Tg) mice that express membrane-associated ovalbumin (mOVA) under the control of a K14 promoter, as well as double Tg mice, by crossing them with OT-I mice that have a TCR recognizing the OVA peptide. When injected with CD8(+) OT-I cells, K14-mOVA Tg mice develop graft-versus-host disease (GVHD), whereas double Tg mice are protected. This suggests that, in double Tg mice, regulatory mechanisms may prevent infused OT-I cells from inducing GVHD. We demonstrated that, after adoptive transfer, TCRalphabeta(+)CD3(+)CD4(-)CD8(-)NK1.1(-) double-negative (DN) T cells are increased in the peripheral lymphoid organs and skin of double Tg mice and exhibit a Valpha2(+)Vbeta5(+)TCR that has the same TCR specificity as OT-I cells. These DN T cells isolated from tolerant double Tg mice proliferated in response to OVA peptide and produced IFN-gamma in the presence of IL-2. These cells could also suppress the proliferation of OT-I cells and were able to specifically kill activated OT-I cells through Fas/Fas ligand interaction. These findings suggest that DN T cells that accumulate in double Tg mice have regulatory functions and may have a role in the maintenance of peripheral tolerance in vivo.
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