Overcoming NK-mediated rejection by anti-3rd-party central memory veto CD8 T cells through downregulation of DNAM-1 on alloreactive NK cells
Summary: Anti-3rd-party central memory veto CD8 T (veto Tcm) cells can overcome T cell-mediated graft rejection under mild conditioning without causing significant graft versus host disease (GVHD). We previously demonstrated that these veto Tcm cells can effectively delete anti-donor T cell clones t...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725004450 |
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| author | Wei-Hsin Liu Aloukick Kumar Singh Christa Blagdon Sandeep Kumar Yadav Einav Shoshan Esther Bachar-Lustig Yair Reisner |
| author_facet | Wei-Hsin Liu Aloukick Kumar Singh Christa Blagdon Sandeep Kumar Yadav Einav Shoshan Esther Bachar-Lustig Yair Reisner |
| author_sort | Wei-Hsin Liu |
| collection | DOAJ |
| description | Summary: Anti-3rd-party central memory veto CD8 T (veto Tcm) cells can overcome T cell-mediated graft rejection under mild conditioning without causing significant graft versus host disease (GVHD). We previously demonstrated that these veto Tcm cells can effectively delete anti-donor T cell clones through a Fas-FasL mechanism, whereas their ability to neutralize alloreactive natural killer (NK) cells and the mechanism of such potential activity remained unknown. Using “nude” mice as recipients of allogeneic T cell-depleted hematopoietic stem cell transplantation (HSCT), we demonstrate effective inhibition of NK-mediated rejection by Tcm cells. Ex vivo studies revealed that Tcm cells express high levels of CD155, the ligand of the activating receptor DNAX accessory molecule-1 (DNAM-1). Conjugate formation between alloreactive NK cells and the veto cells induces NK anergy through a unique mechanism mediated by DNAM-1 internalization and degradation. These insights on veto Tcm cells and their impact on alloreactive NK cells offer potential translational approaches for haploidentical bone marrow transplantation and off-the-shelf chimeric antigen receptor (CAR) cell therapies. |
| format | Article |
| id | doaj-art-19c473e0f4cf4fd39608c7995120ec0b |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-19c473e0f4cf4fd39608c7995120ec0b2025-08-20T03:48:50ZengElsevierCell Reports2211-12472025-05-0144511567410.1016/j.celrep.2025.115674Overcoming NK-mediated rejection by anti-3rd-party central memory veto CD8 T cells through downregulation of DNAM-1 on alloreactive NK cellsWei-Hsin Liu0Aloukick Kumar Singh1Christa Blagdon2Sandeep Kumar Yadav3Einav Shoshan4Esther Bachar-Lustig5Yair Reisner6Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The University of Texas MD Anderson UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USADepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Immunology and Regenerative Biology Department, Weizmann Institute of Science, Rehovot, Israel; Corresponding authorSummary: Anti-3rd-party central memory veto CD8 T (veto Tcm) cells can overcome T cell-mediated graft rejection under mild conditioning without causing significant graft versus host disease (GVHD). We previously demonstrated that these veto Tcm cells can effectively delete anti-donor T cell clones through a Fas-FasL mechanism, whereas their ability to neutralize alloreactive natural killer (NK) cells and the mechanism of such potential activity remained unknown. Using “nude” mice as recipients of allogeneic T cell-depleted hematopoietic stem cell transplantation (HSCT), we demonstrate effective inhibition of NK-mediated rejection by Tcm cells. Ex vivo studies revealed that Tcm cells express high levels of CD155, the ligand of the activating receptor DNAX accessory molecule-1 (DNAM-1). Conjugate formation between alloreactive NK cells and the veto cells induces NK anergy through a unique mechanism mediated by DNAM-1 internalization and degradation. These insights on veto Tcm cells and their impact on alloreactive NK cells offer potential translational approaches for haploidentical bone marrow transplantation and off-the-shelf chimeric antigen receptor (CAR) cell therapies.http://www.sciencedirect.com/science/article/pii/S2211124725004450CP: Immunology |
| spellingShingle | Wei-Hsin Liu Aloukick Kumar Singh Christa Blagdon Sandeep Kumar Yadav Einav Shoshan Esther Bachar-Lustig Yair Reisner Overcoming NK-mediated rejection by anti-3rd-party central memory veto CD8 T cells through downregulation of DNAM-1 on alloreactive NK cells Cell Reports CP: Immunology |
| title | Overcoming NK-mediated rejection by anti-3rd-party central memory veto CD8 T cells through downregulation of DNAM-1 on alloreactive NK cells |
| title_full | Overcoming NK-mediated rejection by anti-3rd-party central memory veto CD8 T cells through downregulation of DNAM-1 on alloreactive NK cells |
| title_fullStr | Overcoming NK-mediated rejection by anti-3rd-party central memory veto CD8 T cells through downregulation of DNAM-1 on alloreactive NK cells |
| title_full_unstemmed | Overcoming NK-mediated rejection by anti-3rd-party central memory veto CD8 T cells through downregulation of DNAM-1 on alloreactive NK cells |
| title_short | Overcoming NK-mediated rejection by anti-3rd-party central memory veto CD8 T cells through downregulation of DNAM-1 on alloreactive NK cells |
| title_sort | overcoming nk mediated rejection by anti 3rd party central memory veto cd8 t cells through downregulation of dnam 1 on alloreactive nk cells |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725004450 |
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