Regulatory dysfunction of the interleukin-2 receptor during HIV infection and the impact of triple combination therapy.
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.
David
D
D
Unité d'Immunogénétique Cellulaire, Département d'Immunologie, Institut Pasteur, Paris, France.
Bani
L
L
Moreau
J L
JL
Treilhou
M P
MP
Nakarai
T
T
Joussemet
M
M
Ritz
J
J
Dupont
B
B
Pialoux
G
G
Thèze
J
J
D001402:B-Lymphocytes / Q000187:drug effects / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D002452:Cell Count / Q000187:drug effects; D002453:Cell Cycle / Q000502:physiology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology
D017320:HIV Protease Inhibitors; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D018894:Reverse Transcriptase Inhibitors