T cell receptor-dependent regulation of lipid rafts controls naive CD8+ T cell homeostasis
T cell receptor (TCR) contact with self ligands keeps T cells alive and is shown here to cause naive CD8(+), but not CD4(+), T cells to be hypersensitive to certain gamma(c) cytokines, notably interleukin (IL)-2, IL-15, and IL-7. Hypersensitivity of CD8(+) T cells to IL-2 was dependent on a low-level TCR signal, associated with high expression of CD5 and GM1, a marker for lipid rafts, and was abolished by disruption of lipid rafts. By contrast, CD4(+) T cells expressed low amounts of GM1 and were unresponsive to IL-2. Physiologically, sensitivity to IL-7 and IL-15 maintains survival of resting CD8(+) T cells, whereas sensitivity to IL-2 may be irrelevant for normal homeostasis but crucial for the immune response. Thus, TCR contact with antigen upregulates GM1 and amplifies responsiveness of naive CD8(+) T cells to IL-2, thereby making the cells highly sensitive to exogenous IL-2 from CD4(+) T helper cells.
|ISBN||1097-4180 (Electronic) 1074-7613 (Linking)|
|Authors||Cho, J. H.; Kim, H. O.; Surh, C. D.; Sprent, J.:|
|DOI||S1074-7613(10)00038-5 [pii] 10.1016/j.immuni.2009.11.014|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20137986|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/10540|