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

Yovana Pacheco, Véronique Solé, Eric Billaud, Clotilde Allavena, Ariane Plet, Virginie Ferré, Laure Garrigue-Antar, François Raffi, Yannick Jacques, Dorian McIlroy
AIDS 2011 September 10, 25 (14): 1701-10

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.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"