Regulation of the human interleukin-2/interleukin-2 receptor system: a role for immunosuppression

The strength of the cellular immune response is regulated to a large extent by the amount of interleukin-2 (IL-2) produced in response to a stimulus. The ability of lymphocytes and other cells to respond to IL-2 depends upon the expression of cell surface IL-2 receptors. Formation of a high-affinity IL-2 receptor is regulated primarily through induction of its alpha subunit, IL-2R alpha. Once formed, the IL-2R alpha chain turns over rapidly, rendering expression of high-affinity IL-2 receptors during the immune response dependent upon continuous activity of the IL-2R alpha gene. The induced expression of both human IL-2 and IL-2R alpha chains is sensitive to cell-mediated suppression by CD8 cells; depletion of CD8 cells leads to extensive superinduction. This coupled suppression of IL-2 and IL-2R alpha genes greatly increases the extent of control, and strongly limits the strength, of the signal transduced by this ligand/receptor system during an immune response.