| First Author | Penaloza-MacMaster P | Year | 2009 |
| Journal | Immunology | Volume | 128 |
| Issue | 2 | Pages | 164-71 |
| PubMed ID | 19740373 | Mgi Jnum | J:162292 |
| Mgi Id | MGI:4818557 | Doi | 10.1111/j.1365-2567.2009.03080.x |
| Citation | Penaloza-MacMaster P, et al. (2009) T-cell reconstitution without T-cell immunopathology in two models of T-cell-mediated tissue destruction. Immunology 128(2):164-71 |
| abstractText | Antigen-specific T cells play a pivotal role in adaptive immune responses. However, they also contribute to the progression of a variety of diseases including autoimmune disorders, graft rejection and graft-versus-host disease (GVHD). Non-specific immune-ablation treatments compromise the ability of the host to respond to infection, whereas the selective removal of epitope-specific T cells could theoretically ameliorate T-cell-mediated pathology while preserving the rest of the host immune function. In this study we investigated whether it is possible to destroy specific unwanted antigen-specific T cells by incubating polyclonal T-cell populations with major histocompatibility complex (MHC) tetramers that are conjugated to the ribosomal-inactivating toxin, saporin. This strategy resulted in a dramatic reduction in the number of targeted antigen (Ag)-specific CD8 T cells with no observable bystander toxicity in vitro. Moreover, in a model of transferable T-cell-dependent neurological disease induced by intracerebral (i.c.) lymphocytic choriomeningitis virus (LCMV) infection, the targeted killing of LCMV-specific CD8 T cells extended the survival of mice or fully prevented their death, depending on the dose of cells transferred. In addition, the tetramer- saporin conjugate also reduced liver damage in a model of donor T-cell-mediated hepatic destruction. These data provide a proof of principle that MHC tetramers could be exploited for the elimination or clinical manipulation of T-cell responses by linking effector molecules (a toxin in this case) to MHC tetramers. Also, the results suggest that it may be feasible to remodel T-cell responses, especially in immunocompromised hosts who receive adoptive cell transfers with many potential alloreactive cells. |
