| First Author | Dervovic DD | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 4 | Pages | 1704-15 |
| PubMed ID | 23851691 | Mgi Jnum | J:205691 |
| Mgi Id | MGI:5546262 | Doi | 10.4049/jimmunol.1300417 |
| Citation | Dervovic DD, et al. (2013) Cellular and molecular requirements for the selection of in vitro-generated CD8 T cells reveal a role for Notch. J Immunol 191(4):1704-15 |
| abstractText | Differentiation of CD8 single-positive (SP) T cells is predicated by the ability of lymphocyte progenitors to integrate multiple signaling cues provided by the thymic microenvironment. In the thymus and the OP9-DL1 system for T cell development, Notch signals are required for progenitors to commit to the T cell lineage and necessary for their progression to the CD4(+)CD8(+) double-positive (DP) stage of T cell development. However, it remains unclear whether Notch is a prerequisite for the differentiation of DP cells to the CD8 SP stage of development. In this study, we demonstrate that Notch receptor-ligand interactions allow for efficient differentiation and selection of conventional CD8 T cells from bone marrow-derived hematopoietic stem cells. However, bone marrow-derived hematopoietic stem cells isolated from Itk(-/-)Rlk(-/-) mice gave rise to T cells with decreased IFN-gamma production, but gained the ability to produce IL-17. We further reveal that positive and negative selection in vitro are constrained by peptide-MHC class I expressed on OP9 cells. Finally, using an MHC class I-restricted TCR-transgenic model, we show that the commitment of DP precursors to the CD8 T cell lineage is dependent on Notch signaling. Our findings further establish the requirement for Notch receptor-ligand interactions throughout T cell differentiation, including the final step of CD8 SP selection. |
