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Role of Immunoregulatory Donor T Cells in Suppression of Graft-Versus-Host Disease Following Donor Leukocyte Infusion Therapy
| Content Provider | Scilit |
|---|---|
| Author | Johnson, Bryon D. Becker, Emily E. LaBelle, James L. Truitt, Robert L. |
| Copyright Year | 1999 |
| Description | In murine models of allogeneic bone marrow transplantation (BMT), MHC-mismatched recipients given a delayed infusion of donor leukocytes (DLI) at 21 days posttransplant develop significant GVHD whereas MHC-matched recipients do not. The current study was initially designed to test the hypothesis that small numbers of T cells in the MHC-mismatched donor bone marrow (BM) graft exacerbated graft-vs-host disease (GVHD) when DLI was administered at 21 days after BMT. Ex vivo depletion of $Thy1^{+}$ cells from the donor BM had no impact on the severity of GVHD after DLI. However, depletion of donor T cells in vivo with a Thy1 allele-specific mAb given after BMT resulted in significantly more severe GVHD after DLI. Similar results were obtained in a MHC-matched model of allogeneic BMT, indicating that this was a general phenomenon and not model dependent. These results indicated that a population of donor-derived $Thy1^{+}$ cells suppressed graft-vs-host reactivity after DLI. Results of experiments with thymectomized recipients demonstrated that an intact thymus was required for generation of the immunoregulatory donor cells. Experiments using TCR β-chain knockout mice as BM donors indicated that the immunosuppressive $Thy1^{+}$ cells coexpressed αβTCR heterodimers. Similar experiments with CD4 and CD8 knockout donor BM suggested that the immunoregulatory $Thy1^{+}αβTCR^{+}$ cells consisted of two subpopulations: a $CD4^{+}CD8^{−}$ subpopulation and a $CD4^{−}CD8^{−}$ subpopulation. Together, these results show that thymus-derived, $Thy1^{+}αβTCR^{+}$ donor cells generated early after allogeneic BMT suppress the graft-vs-host reactivity of T cells given as DLI. These cells may mediate dominant peripheral tolerance after allogeneic BMT. |
| Ending Page | 6487 |
| Page Count | 9 |
| Starting Page | 6479 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.163.12.6479 |
| Journal | The Journal of Immunology |
| Issue Number | 12 |
| Volume Number | 163 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 1999-12-15 |
| Access Restriction | Open |
| Subject Keyword | Cell Tissue Engineering Bone Marrow Immunoregulatory Donor T Cells Cells Suppressed Host Reactivity Mhc Matched |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
