Defective interleukin-2-dependent STAT5 signalling in CD8 T lymphocytes from HIV-positive patients: restoration by antiretroviral therapy

AIDS. 2004 Feb 20;18(3):421-6. doi: 10.1097/00002030-200402200-00007.


Background: CD8 T lymphocytes are critical in the control of HIV replication and disease progression. Our previous studies demonstrated that CD8 T cells from chronically infected patients with high virus load proliferated poorly in response to interleukin-2 (IL-2), a cytokine critical in CD8 T cell growth and differentiation, even though relatively high levels of IL-2 receptor (IL-2R) were expressed. This suggested that signal transduction defects in response to IL-2 might be involved. The STAT5 transcription factor is important in IL-2-dependent biological responses and it is known that there are defects in unstimulated CD3 and CD4 cells in HIV-infected patients.

Objective: To investigate whether the induction of STAT5 by IL-2 is altered in the CD8 T cells from HIV-positive individuals and the impact of highly active antiretroviral therapy (HAART) on its status.

Methods: CD8 T lymphocytes were purified from the peripheral blood mononuclear cells of HIV-positive patients before and after HAART. Ex vivo IL-2-induced STAT5 activation was evaluated by immunoblotting and electrophoretic mobility shift assays.

Results: CD8 T cells from a subset of untreated HIV-positive patients were unable to activate STAT5a and STAT5b proteins functionally in response to IL-2. This defect was not a result of alterations in IL-2R expression but correlated with an impaired activation of the upstream kinase Jak-3, known to mediate STAT5 activation. Overall, HAART restored Jak/STAT signalling in such patients.

Conclusions: These results further uncover a potential mechanism by which CD8 T cell function is impaired in HIV-infected patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiretroviral Therapy, Highly Active*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • DNA-Binding Proteins / immunology*
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • Humans
  • Interleukin-2 / immunology*
  • Janus Kinase 3
  • Milk Proteins*
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Interleukin-2 / blood
  • STAT5 Transcription Factor
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Trans-Activators / immunology*
  • Tumor Suppressor Proteins


  • DNA-Binding Proteins
  • Interleukin-2
  • Milk Proteins
  • Receptors, Interleukin-2
  • STAT5 Transcription Factor
  • STAT5A protein, human
  • STAT5B protein, human
  • Trans-Activators
  • Tumor Suppressor Proteins
  • Protein-Tyrosine Kinases
  • JAK3 protein, human
  • Janus Kinase 3