Mechanisms of Tolerance Induced by Donor-Specific Transfusion and ICOS-B7h Blockade in a Model of CD4+ T-Cell-Mediated Allograft Rejection

Content Provider	Scilit
Author	Sandner, Sigrid E. Clarkson, Michael R. Salama, Alan D. Sanchez-Fueyo, Alberto Yagita, Hideo Turka, Laurence A. Sayegh, Mohamed H.
Copyright Year	2005
Description	Journal: American Journal of Transplantation The inducible co-stimulatory molecule (ICOS) has been shown to play a critical role in T-cell activation and differentiation, and the regulation of alloimmune responses in vivo. Using an MHC class II mismatched model of CD4(+) T-cell-mediated rejection, we found that treatment of mice with DST and ICOS-B7h blockade induced long-term skin allograft survival and donor-specific transplantation tolerance. ICOS blockade, either during antigen priming or during the effector phase, previously shown to alter the outcome of the immune response, had a similar effect on graft survival. DST and anti-B7h mAb reduced the frequency of IFN-gamma-producing allospecific cells but did not produce deviation to a T(H)2 phenotype. In an adoptive transfer model using ABM TCR transgenic mice directly reactive to I-A(bm12), DST and anti-B7h mAb reduced the number of allospecific CD4(+) T cells and increased CD4(+) T-cell apoptosis. These data demonstrate that DST and anti-B7h mAb induces transplantation tolerance to MHC class II mismatched skin grafts by a reduction of the alloreactive clone size that is, at least in part, dependent on apoptosis of host alloantigen-specific CD4(+) T cells.
Related Links	http://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2004.00640.x/pdf
Ending Page	39
Page Count	9
Starting Page	31
e-ISSN	16006143
DOI	10.1111/j.1600-6143.2004.00640.x
Journal	American Journal of Transplantation
Issue Number	1
Volume Number	5
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2005-01-01
Access Restriction	Open
Subject Keyword	Journal: American Journal of Transplantation
Content Type	Text
Resource Type	Article