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.
Immunology and Inflammation Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia.
Jae-Ho
JH
Cho
Hee-Ok
HO
Kim
Charles D
CD
Surh
Jonathan
J
Sprent
D000818:Animals; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D006028:Glycosphingolipids / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006649:Histocompatibility Antigens / Q000378:metabolism; D006706:Homeostasis; D053631:Interleukin Receptor Common gamma Subunit / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D001324:Autoantigens; D016207:Cytokines; D006028:Glycosphingolipids; D006649:Histocompatibility Antigens; D053631:Interleukin Receptor Common gamma Subunit; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell