Induction of interleukin-2 unresponsiveness and down-regulation of the JAK-STAT system upon activation through the T cell receptor.

Full activation of T cells with antigen (Ag) and antigen-presenting cells initiates effector functions and proliferation. When T cells are re-stimulated through the T cell receptor (TCR) after a primary stimulation with Ag, growth arrest and cell death are induced. Activation of a T cell clone by cross-linking of TCR induces interleukin (IL)-2 unresponsiveness and ultimately cell death. While the proliferative signal delivered by IL-2 induces c-myc, bcl-2 and cyclin D3 expression, the expression of bcl-2 and cyclin D3 is completely suppressed upon TCR stimulation. Furthermore, TCR stimulation induces a decrease in the protein levels of JAK3 and STAT5, suggesting that IL-2 unresponsiveness and growth arrest of T cells result from down-regulation of JAK3 and STAT5.