| First Author | Honda T | Year | 2014 |
| Journal | Immunity | Volume | 40 |
| Issue | 2 | Pages | 235-247 |
| PubMed ID | 24440150 | Mgi Jnum | J:209370 |
| Mgi Id | MGI:5567029 | Doi | 10.1016/j.immuni.2013.11.017 |
| Citation | Honda T, et al. (2014) Tuning of antigen sensitivity by T cell receptor-dependent negative feedback controls T cell effector function in inflamed tissues. Immunity 40(2):235-47 |
| abstractText | Activated T cells must mediate effector responses sufficiently to clear pathogens while avoiding excessive tissue damage. Here we have combined dynamic intravital microscopy with ex vivo assessments of T cell cytokine responses to generate a detailed spatiotemporal picture of CD4(+) T cell effector regulation in the skin. In response to antigen, effector T cells arrested transiently on antigen-presenting cells, briefly producing cytokine and then resuming migration. Antigen recognition led to upregulation of the programmed death-1 (PD-1) glycoprotein by T cells and blocking its canonical ligand, programmed death-ligand 1 (PD-L1), lengthened the duration of migration arrest and cytokine production, showing that PD-1 interaction with PD-L1 is a major negative feedback regulator of antigen responsiveness. We speculate that the immune system employs T cell recruitment, transient activation, and rapid desensitization to allow the T cell response to rapidly adjust to changes in antigen presentation and minimize collateral injury to the host. |
