Despite an impaired response to IL-7, CD4+EM T cells from HIV-positive patients proliferate normally in response to IL-15 and its superagonist, RLI

AIDS. 2011 Sep 10;25(14):1701-10. doi: 10.1097/QAD.0b013e328349a437.


Objective: In phase I/II trials, IL-7 immunotherapy has been shown to expand CD4(+) T cells. However, expression of the IL-7 receptor α-chain, CD127, is reduced on CD4(+) T cells from HIV-positive patients, and defects in CD127 signaling have also been reported. To refine and improve cytokine immunotherapy, it is important to identify stimuli that can restore proliferation of CD4(+) cells with defective responses to IL-7.

Design: Observational study comparing viremic HIV-positive patients with HIV-negative controls.

Methods: Peripheral blood mononuclear cells were cultured in the presence of 1 nmol/l IL-2, IL-7, IL-15 or RLI (an IL-15Rα/IL-15 fusion protein). Proliferation of different T-cell subsets was assessed by carboxyfluorescein succinimidyl ester fluorescence. Expression of CD127 on CD4(+) T-cell subsets was also analyzed.

Results: In HIV-positive patients, CD127 expression was correlated with CD4(+) T-cell count in the CD4(+)(N) (R(2) = 0.36; P < 0.01) and CD4(+)(CM) (R(2) = 0.45; P < 0.001) populations, whereas CD127 expression on CD4(+)(EM) cells was significantly reduced in HIV-positive individuals compared with controls (P = 0.001) independently of CD4(+) T-cell count. In patients with high CD4(+) T-cell counts, proliferation in response to IL-7 was significantly reduced only in CD4(+)(EM) cells (P < 0.05). RLI, and to a lesser extent IL-15, induced strong proliferation of CD4(+)(EM) cells from both HIV-positive patients and controls. Neither agent stimulated proliferation of CD4(+)(N) or CD4(+)(CM) cells.

Conclusion: In HIV-positive patients, CD4(+)(EM) cells are deficient in both CD127 expression and proliferation in response to IL-7. RLI and IL-15 specifically induced proliferation of CD4(+)(EM) cells, suggesting that they may have a unique potential to complement IL-7 immunotherapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacology*
  • Apoptosis / drug effects
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Humans
  • Interleukin-15 / immunology
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Receptors, Interleukin-15 / agonists*
  • Receptors, Interleukin-15 / genetics
  • Receptors, Interleukin-15 / immunology*
  • Receptors, Interleukin-7 / drug effects
  • Receptors, Interleukin-7 / genetics
  • Receptors, Interleukin-7 / immunology*
  • Recombinant Fusion Proteins / immunology*


  • Anti-HIV Agents
  • IL-15Ralpha-sushi domain-linker-IL-15 fusion protein
  • IL15RA protein, human
  • Interleukin-15
  • Receptors, Interleukin-15
  • Receptors, Interleukin-7
  • Recombinant Fusion Proteins