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A Novel Alloantigen-Specific CD8+PD1+ Regulatory T Cell Induced by ICOS-B7h Blockade In Vivo
| Content Provider | Scilit |
|---|---|
| Author | Izawa, Atsushi Yamaura, Kazuhiro Albin, Monica J. Jurewicz, Mollie Tanaka, Katsunori Clarkson, Michael R. Ueno, Takuya Habicht, Antje Freeman, Gordon J. Yagita, Hideo Abdi, Reza Pearson, Todd Greiner, Dale L. Sayegh, Mohamed H. Najafian, Nader |
| Copyright Year | 2007 |
| Description | 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-γ 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. |
| Ending Page | 796 |
| Page Count | 11 |
| Starting Page | 786 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.179.2.786 |
| Journal | The Journal of Immunology |
| Issue Number | 2 |
| Volume Number | 179 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2007-07-15 |
| Access Restriction | Open |
| Subject Keyword | Cell Tissue Engineering Cell Induced Blockade in Vivo Induced By Icos |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
