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Donor CD8+ T Cells Mediate Graft-versus-Leukemia Activity without Clinical Signs of Graft-versus-Host Disease in Recipients Conditioned with Anti-CD3 Monoclonal Antibody
| Content Provider | Scilit |
|---|---|
| Author | Zhang, Chunyan Lou, Jingwei Li, Nainong Todorov, Ivan Lin, Chia-Lei Cao, Yu-An Contag, Christopher H. Kandeel, Fouad Forman, Stephen Zeng, Defu |
| Copyright Year | 2007 |
| Description | Donor $CD8^{+}$ T cells play a critical role in mediating graft-vs-leukemia (GVL) activity, but also induce graft-vs-host disease (GVHD) in recipients conditioned with total body irradiation (TBI). In this study, we report that injections of donor C57BL/6 $(H-2^{b}$) or FVB/N $(H-2^{q}$) $CD8^{+}$ T with bone marrow cells induced chimerism and eliminated BCL1 leukemia/lymphoma cells without clinical signs of GVHD in anti-CD3-conditioned BALB/c $(H-2^{d}$) recipients, but induced lethal GVHD in TBI-conditioned recipients. Using in vivo and ex vivo bioluminescent imaging, we observed that donor $CD8^{+}$ T cells expanded rapidly and infiltrated GVHD target tissues in TBI-conditioned recipients, but donor $CD8^{+}$ T cell expansion in anti-CD3-conditioned recipients was confined to lymphohematological tissues. This confinement was associated with lack of up-regulated expression of $α_{4}β_{7}$ integrin and chemokine receptors (i.e., CXCR3) on donor $CD8^{+}$ T cells. In addition, donor $CD8^{+}$ T cells in anti-CD3-conditioned recipients were rendered unresponsive, anergic, $Foxp3^{+}$, or type II cytotoxic T phenotype. Those donor $CD8^{+}$ T cells showed strong suppressive activity in vitro and mediated GVL activity without clinical signs of GVHD in TBI-conditioned secondary recipients. These results indicate that anti-CD3 conditioning separates GVL activity from GVHD via confining donor $CD8^{+}$ T cell expansion to host lymphohemological tissues as well as tolerizing them in the host. |
| Ending Page | 850 |
| Page Count | 13 |
| Starting Page | 838 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.178.2.838 |
| Journal | The Journal of Immunology |
| Issue Number | 2 |
| Volume Number | 178 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2007-01-15 |
| Access Restriction | Open |
| Subject Keyword | Cell Tissue Engineering Bone Marrow Anti Cd3 Conditioned Recipients |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
