Interleukin‐2 receptor β and γ chain dysregulation during the inhibition of CD4 T cell activation by human immunodeficiency virus‐1 gp120

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Abstract
We have observed that CD4 T lymphocytes from human immunodeficiency virus (HIV)‐infected patients marginally express interleukin‐2 receptor (IL‐2R)β and IL‐2Rγ chains which are essential for IL‐2 signal transduction. To analyze this observation further, we studied the influence of gp120 on the cell surface expression of IL‐2Rβ and IL‐2Rγ by purified CD4 lymphocytes in vitro. Cross‐linking of the T cell receptors of these lymphocytes initiates entry into the cell cycle as measured by CD69 and CD71 cell surface expression and [3H]thymidine incorporation. It also induces the cell surface expression of IL‐2Rβ and IL‐2Rγ. We have shown that treatment of the CD4 T lymphocytes with HIV‐1 gp120 before anti‐CD3 stimulation impedes cell cycle progression as measured by reduced CD71 expression and inhibition of [3H]thymidine incorporation. Furthermore, cell surface expression of IL‐2Rβ and IL‐2Rγ subunits, which form the functional intermediate‐affinity IL‐2R, are significantly inhibited. More importantly, addition of exogenous IL‐2 does not restore the proliferation of the CD4 T cells treated with gp120, suggesting that cells are anergic and/or that the remaining IL‐2R are not functional. This is the first study of IL‐2Rβ and IL‐2Rγ dysregulation in the context of HIV infection and shows that CD4 is also involved in IL‐2R expression.

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