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Ex Vivo Anti-CD3 Antibody-Activated Donor T Cells Have a Reduced Ability to Cause Lethal Murine Graft-Versus-Host Disease but Retain Their Ability to Facilitate Alloengraftment
| Content Provider | Scilit |
|---|---|
| Author | Drobyski, William R. Majewski, David Ozker, Kutlan Hanson, Gerald |
| Copyright Year | 1998 |
| Abstract | The purpose of this study was to determine whether ex vivo anti-CD3 Ab-activated T cells behaved in a biologically similar manner as naive T cells with respect to causing graft-vs-host disease (GVHD) and facilitating engraftment after allogeneic marrow transplantation. This question was addressed using two well-defined MHC-incompatible murine models of GVHD (C57BL/6 $(H-2^{b}$)→B10.BR $(H-2^{k}$)) and engraftment (C57BL/6 $(H-2^{b}$)→AKR/J $(H-2^{k}$)). Transplantation with anti-CD3-activated T cells significantly reduced GVHD compared with that in animals transplanted with equivalent numbers of naive T cells. Protection from GVHD was not T cell subset dependent, as highly enriched populations of either activated $CD4^{+}$ or $CD8^{+}$ T cells caused less lethal GVHD than comparable numbers of purified naive $CD4^{+}$ or $CD8^{+}$ T cells. Transplantation with activated T cells also resulted in protection from LPS-mediated GVH lethality in unirradiated $F_{1}$ recipients. Analysis of immune recovery indicated that animals transplanted with activated T cells had thymic and splenic B cell reconstitution that compared favorably to that in non-GVHD control mice. When engraftment was analyzed, equivalent degrees of donor cell engraftment were observed when animals were transplanted with limiting numbers (5 × $10^{5}$) of naive vs activated B6 T cells. Further studies indicated that activated $CD8^{+}$ T cells were exclusively responsible for enhancing engraftment and that facilitation of engraftment was dependent upon the direct recognition of host MHC alloantigens. Collectively, these data demonstrate that transplantation with anti-CD3 Ab-activated T cells results in a reduction in GVHD, but these cells retain their ability to facilitate alloengraftment. The use of this approach in allogeneic marrow transplantation may represent an alternative strategy to mitigate GVHD without compromising engraftment. |
| Ending Page | 2619 |
| Page Count | 10 |
| Starting Page | 2610 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.161.5.2610 |
| Journal | The Journal of Immunology |
| Issue Number | 5 |
| Volume Number | 161 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 1998-09-01 |
| Access Restriction | Open |
| Subject Keyword | Cell Tissue Engineering Donor Cell Ab Activated T Cells Anti Cd3 Ab Activated |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
