Human immunodeficiency virus‐1 envelope glycoproteins and anti‐CD4 antibodies inhibit interleukin‐2‐induced Jak/STAT signalling in human CD4 T lymphocytes

Summary Human immunodeficiency virus (HIV) infection leads to a profound T cell dysfunction well before the clinical onset of acquired immunodeficiency syndrome (AIDS). We have been accumulating evidence that one of the mechanisms responsible for this T cell deficiency may be the dysregulation of signal transduction via the interleukin (IL)‐2/IL‐2 receptor (R) complex. In CD4 T cells, we have observed previously that viral envelope (env) glycoproteins induce IL‐2 unresponsiveness and the down‐regulation of the three chains making up the IL‐2R ( α , β , γ ) in vitro . We have now established further that this disruption of the IL‐2/IL‐2R system manifests itself in defective signal propagation via the Janus kinase (Jak)/signal transducer and activator of transcription (STAT) pathway in response to IL‐2. The treatment of CD4 T cells with HIV env or surface ligation of CD4 with anti‐CD4 monoclonal antibodies inhibited the IL‐2‐induced activation of Jak‐1 and Jak‐3, as well as their targets, STAT5a and STAT5b. This Jak/STAT deficiency may contribute to the crippling of CD4 T cell responses to a cytokine central to the immune response by HIV.