| First Author | Sullivan SA | Year | 2014 |
| Journal | J Immunol | Volume | 192 |
| Issue | 6 | Pages | 2865-74 |
| PubMed ID | 24523509 | Mgi Jnum | J:209918 |
| Mgi Id | MGI:5568906 | Doi | 10.4049/jimmunol.1302493 |
| Citation | Sullivan SA, et al. (2014) The role of LAT-PLCgamma1 interaction in gammadelta T cell development and homeostasis. J Immunol 192(6):2865-74 |
| abstractText | LAT is a transmembrane adaptor protein that is vital for integrating TCR-mediated signals to modulate T cell development, activation, and proliferation. Upon T cell activation, LAT is phosphorylated and associates with Grb2, Gads, and PLCgamma1 through its four distal tyrosine residues. Mutation of one of these tyrosines, Y136, abolishes LAT binding to PLCgamma1. This results in impaired TCR-mediated calcium mobilization and Erk activation. CD4 alphabeta T cells in LATY136F knock-in mice undergo uncontrolled expansion, resulting in a severe autoimmune syndrome. In this study, we investigated the importance of the LAT-PLCgamma1 interaction in gammadelta T cells by crossing LATY136F mice with TCRbeta(-/-) mice. Our data showed that the LATY136F mutation had no major effect on homeostasis of epithelial gammadelta T cells, which could be found in the skin and small intestine. Interestingly, a population of CD4(+) gammadelta T cells in the spleen and lymph nodes underwent continuous expansion and produced elevated amounts of IL-4, resulting in an autoimmune syndrome similar to that caused by alphabeta T cells in LATY136F mice. Development of these hyperproliferative gammadelta T cells was not dependent on MHC class II expression or CD4, and their proliferation could be suppressed, in part, by regulatory T cells. Our data indicated that a unique subset of CD4 gammadelta T cells can hyperproliferate in LATY136F mice and suggested that LAT-PLCgamma1 signaling may function differently in various subsets of gammadelta T cells. |
