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.
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