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

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Abstract
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.