| First Author | Matson CA | Year | 2020 |
| Journal | Proc Natl Acad Sci U S A | Volume | 117 |
| Issue | 25 | Pages | 14342-14353 |
| PubMed ID | 32513716 | Mgi Jnum | J:294360 |
| Mgi Id | MGI:6437637 | Doi | 10.1073/pnas.1922525117 |
| Citation | Matson CA, et al. (2020) CD5 dynamically calibrates basal NF-kappaB signaling in T cells during thymic development and peripheral activation. Proc Natl Acad Sci U S A 117(25):14342-14353 |
| abstractText | Immature T cells undergo a process of positive selection in the thymus when their new T cell receptor (TCR) engages and signals in response to self-peptides. As the T cell matures, a slew of negative regulatory molecules, including the inhibitory surface glycoprotein CD5, are up-regulated in proportion to the strength of the self-peptide signal. Together these regulators dampen TCR-proximal signaling and help avoid any subsequent peripheral activation of T cells by self-peptides. Paradoxically, antigen-specific T cells initially expressing more CD5 (CD5(hi)) have been found to better persist as effector/memory cells after a peripheral challenge. The molecular mechanisms underlying such a duality in CD5 function is not clear. We found that CD5 alters the basal activity of the NF-kappaB signaling in resting peripheral T cells. When CD5 was conditionally ablated, T cells were unable to maintain higher expression of the cytoplasmic NF-kappaB inhibitor IkappaBalpha. Consistent with this, resting CD5(hi) T cells expressed more of the NF-kappaB p65 protein than CD5(lo) cells, without significant increases in transcript levels, in the absence of TCR signals. This posttranslationally stabilized cellular NF-kappaB depot potentially confers a survival advantage to CD5(hi) T cells over CD5(lo) ones. Taken together, these data suggest a two-step model whereby the strength of self-peptide-induced TCR signal lead to the up-regulation of CD5, which subsequently maintains a proportional reserve of NF-kappaB in peripheral T cells poised for responding to agonistic antigen-driven T cell activation. |
