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Opposing Effects of ICOS on Graft-versus-Host Disease Mediated by CD4 and CD8 T Cells
| Content Provider | Scilit |
|---|---|
| Author | Yu, Xue-Zhong Liang, Yaming Nurieva, Roza I. Guo, Fei Anasetti, Claudio Dong, Chen |
| Copyright Year | 2006 |
| Description | ICOS, a CD28 family member expressed on activated $CD4^{+}$ and $CD8^{+}$ T cells, plays important roles in T cell activation and effector function. Here we studied the role of ICOS in graft-vs-host disease (GVHD) mediated by $CD4^{+}$ or $CD8^{+}$ T cells in allogeneic bone marrow transplantation. In comparison of wild-type and ICOS-deficient T cells, we found that recipients of $ICOS^{−/−}$ $CD4^{+}$ T cells exhibited significantly less GVHD morbidity and delayed mortality. $ICOS^{−/−}$ $CD4^{+}$ T cells had no defect in expansion, but expressed significantly less Fas ligand and produced significantly lower levels of IFN-γ and TNF-α. Thus, $ICOS^{−/−}$ $CD4^{+}$ T cells were impaired in effector functions that lead to GVHD. In contrast, recipients of $ICOS^{−/−}$ $CD8^{+}$ T cells exhibited significantly enhanced GVHD morbidity and accelerated mortality. In the absence of ICOS signaling, either using ICOS-deficient donors or ICOS ligand-deficient recipients, the levels of expansion and Tc1 cytokine production of $CD8^{+}$ T cells were significantly increased. The level of expansion was inversely correlated with the level of apoptosis, suggesting that increased ability of $ICOS^{−/−}$ $CD8^{+}$ T cells to induce GVHD resulted from the enhanced survival and expansion of those cells. Our findings indicate that ICOS has paradoxical effects on the regulation of alloreactive $CD4^{+}$ and $CD8^{+}$ T cells in GVHD. |
| Ending Page | 7401 |
| Page Count | 8 |
| Starting Page | 7394 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.176.12.7394 |
| Journal | The Journal of Immunology |
| Issue Number | 12 |
| Volume Number | 176 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2006-06-15 |
| Access Restriction | Open |
| Subject Keyword | Bone Marrow Icos Deficient Effector Function |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
