| First Author | Katzman SD | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 42 | Pages | 18085-90 |
| PubMed ID | 20921406 | Mgi Jnum | J:165535 |
| Mgi Id | MGI:4837611 | Doi | 10.1073/pnas.1010560107 |
| Citation | Katzman SD, et al. (2010) Duration of antigen receptor signaling determines T-cell tolerance or activation. Proc Natl Acad Sci U S A 107(42):18085-90 |
| abstractText | The early events that determine the decision between lymphocyte tolerance and activation are not well-understood. Using a model of systemic self-antigen recognition by CD4(+) T cells, we show, using single-cell biochemical analyses, that tolerance is characterized by transient signaling events downstream of T-cell receptor engagement in the mammalian target of rapamycin (mTOR) and NF-kappaB pathways. Parallel studies done by live cell imaging show that the key difference between tolerance and activation is the duration of the T cell-antigen presenting cell (APC) interaction, as revealed by stable T-cell immobilization on antigen encounter. Brief T cell-APC interactions result in tolerance, and prolonged interactions are associated with activation and the development of effector cells. These studies show that the duration of T cell-APC interactions and magnitude of associated TCR-mediated signaling are key determinants of lymphocyte tolerance vs. activation. |
