A novel alloantigen-specific CD8+PD1+ regulatory T cell induced by ICOS-B7h blockade in vivo
Biochemistry & Molecular Pharmacology
Graduate School of Biomedical Sciences; Department of Medicine, Diabetes Division
Life Sciences | Medicine and Health Sciences
Delayed ICOS-B7h signal blockade promotes significant prolongation of cardiac allograft survival in wild-type but not in CD8-deficient C57BL/6 recipients of fully MHC-mismatched BALB/c heart allografts, suggesting the possible generation of CD8(+) regulatory T cells in vivo. We now show that the administration of a blocking anti-ICOS mAb results in the generation of regulatory CD8(+) T cells. These cells can transfer protection and prolong the survival of donor-specific BALB/c, but not third party C3H, heart grafts in CD8-deficient C57BL/6 recipients. This is unique to ICOS-B7h blockade, because B7 blockade by CTLA4-Ig prolongs graft survival in CD8-deficient mice and does not result in the generation of regulatory CD8(+) T cells. Those cells localize to the graft, produce both IFN-gamma and IL-4 after allostimulation in vitro, prohibit the expansion of alloreactive CD4(+) T cells, and appear to mediate a Th2 switch of recipient CD4(+) T cells after adoptive transfer in vivo. Finally, these cells are not confined to the CD28-negative population but express programmed death 1, a molecule required for their regulatory function in vivo. CD8(+)PD1(+) T cells suppress alloreactive CD4(+) T cells but do not inhibit the functions by alloreactive CD8(+) T cells in vitro. These results describe a novel allospecific regulatory CD8(+)PD1(+) T cell induced by ICOS-B7h blockade in vivo.
DOI of Published Version
J Immunol. 2007 Jul 15;179(2):786-96.
Journal of immunology (Baltimore, Md. : 1950)
Izawa A, Yamaura K, Albin MJ, Jurewicz M, Tanaka K, Clarkson MR, Ueno T, Habicht A, Freeman GJ, Yagita H, Abdi R, Pearson T, Greiner DL, Sayegh MH, Najafian N. (2007). A novel alloantigen-specific CD8+PD1+ regulatory T cell induced by ICOS-B7h blockade in vivo. GSBS Student Publications. https://doi.org/10.4049/jimmunol.179.2.786. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/567