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

作者：Pacheco Yovana; Sole Veronique; Billaud Eric; Allavena Clotilde; Plet Ariane; Ferre Virginie; Garrigue Antar Laure; Raffi Francois; Jacques Yannick; McIlroy Dorian^*

来源：AIDS, 2011, 25(14): 1701-1710.

DOI：10.1097/QAD.0b013e328349a437

• cytokines
• HIV
• immunotherapy
• interleukin-15
• interleukin-7
• T lymphocytes

Objective: In phase I/II trials, IL-7 immunotherapy has been shown to expand CD4(+)T cells. However, expression of the IL-7 receptor a-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/ vertical bar IL-2, IL-7, IL-15 or RLI (an IL-15Ra alpha/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.

• 出版日期2011-9-10