Open AccessRegulatory dysfunction of the interleukin-2 receptor during HIV infection and the impact of triple combination therapy
Author(s) -
Denis David,
Lynda Bani,
JeanLouis Moreau,
Marie-Pierre Treilhou,
Takayuki Nakarai,
M. Joussemet,
Jérôme Ritz,
B. Dupont,
Gilles Pialoux,
Jacques Thèze
Publication year - 1998
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.95.19.11348
Subject(s) - immunology , interleukin 2 , cd8 , viral load , receptor , immunity , biology , receptor expression , immunotherapy , interleukin , immune system , medicine , human immunodeficiency virus (hiv) , cytokine
The interleukin-2 (IL-2)/IL-2 receptor (IL-2R) system is the main regulatory determinant of T cell reactivity. Although it is well known that IL-2 secretion is impaired during HIV infection, up to now IL-2R expression has not been extensively studied in HIV-infected patients despite the use of IL-2 in clinical therapy trials. We show here that IL-2R expression in HIV patients with high viral load (group 1 in the study) is greatly enhanced on B lymphocytes, CD8 T lymphocytes, and monocytes, but not on CD4 T lymphocytes, compared with noninfected individuals. Paradoxically, this modified IL-2R expression does not lead to increased IL-2 responsiveness, except for B lymphocytes. In patients receiving triple combination therapy (TCT, two reverse transcriptase inhibitors and one protease inhibitor) that has triggered a drastic reduction in plasma viral load and an increase in CD4 counts (group 2 patients), IL-2R expression is significantly lower than in group 1 patients. Moreover, cells involved in cellular immunity and CD4 T lymphocytes have the capacity to respond to IL-2 after TCT. These results allow us to anticipate a beneficial role of IL-2 immunotherapy in combination with TCT.