| First Author | Chuck MI | Year | 2010 |
| Journal | J Immunol | Volume | 184 |
| Issue | 5 | Pages | 2476-86 |
| PubMed ID | 20130215 | Mgi Jnum | J:159644 |
| Mgi Id | MGI:4452194 | Doi | 10.4049/jimmunol.0902876 |
| Citation | Chuck MI, et al. (2010) The role of the LAT-PLC-gamma1 interaction in T regulatory cell function. J Immunol 184(5):2476-86 |
| abstractText | The interaction between the linker for activation of T cells (LAT) with PLC-gamma1 is important for TCR-mediated Ca(2+) signaling and MAPK activation. Knock-in mice harboring a mutation at the PLC-gamma1 binding site (Y136) of LAT develop a severe lymphoproliferative syndrome. These mice have defective thymic development and selection and lack natural regulatory T cells, implicating a breakdown of both central and peripheral tolerance. To bypass this developmental defect, we developed a conditional knock-in line in which only LATY136F is expressed in mature T cells after deletion of the wild type LAT allele. Analysis of LATY136F T cells indicated that the interaction between LAT and PLC-gamma1 plays an important role in TCR-mediated signaling, proliferation, and IL-2 production. Furthermore, the deletion of LAT induced development of the lymphoproliferative syndrome in these mice. Although Foxp3(+) natural Treg cells were present in these mice after deletion, they were unable to suppress the proliferation of conventional T cells. Our data indicate that the binding of LAT to PLC-gamma1 is essential for the suppressive function of CD4(+)CD25(+) regulatory T cells. |
