| First Author | Watanabe N | Year | 2000 |
| Journal | J Immunol | Volume | 165 |
| Issue | 11 | Pages | 6252-61 |
| PubMed ID | 11086060 | Mgi Jnum | J:112138 |
| Mgi Id | MGI:3655577 | Doi | 10.4049/jimmunol.165.11.6252 |
| Citation | Watanabe N, et al. (2000) The quantity of TCR signal determines positive selection and lineage commitment of T cells. J Immunol 165(11):6252-61 |
| abstractText | It is generally accepted that the avidity of TCR for self Ag/MHC determines the fate of immature thymocytes. However, the contribution of the quantity of TCR signal to T cell selection has not been well established, particularly in vivo. To address this issue, we analyzed DO-TCR transgenic CD3zeta-deficient (DO-Tg/zetaKO) mice in which T cells have a reduced TCR on the cell surface. In DO-Tg/zetaKO mice, very few CD4 single positive (SP) thymocytes developed, indicating that the decrease in TCR signaling resulted in a failure of positive selection of DO-Tg thymocytes. Administration of the peptide Ag to DO-Tg/zetaKO mice resulted in the generation of functional CD4 SP mature thymocytes in a dose-dependent manner, and, unexpectedly, DO-Tg CD8 SP cells emerged at lower doses of Ag. TCR signal-dependent, sequential commitment from CD8(+) SP to CD4(+) SP was also shown in a class I-restricted TCR-Tg system. These in vivo analyses demonstrate that the quantity of TCR signal directly determines positive and negative selection, and further suggest that weak signal directs positively selected T cells to CD8 lineage and stronger signal to CD4 lineage. |
