Anti-retroviral therapy in HIV-infected patients: in vitro effects of AZT and saquinavir on the response of CD4 and CD8 lymphocytes to interleukin-7.
IL-7 is a crucial cytokine regulating lymphopoiesis and peripheral T lymphocyte homeostasis. Plasma IL-7 levels increase during HIV infection and, although antiretroviral therapy (ARV therapy) decreases these levels, they fail to return to normal. Immune reconstitution in most ARV-treated patients is only partial. We tested the possibility that the IL-7R system might be affected by ARV drugs. The effects of the antireverse transcriptase AZT and the anti-protease saquinavir on CD3- and CD3+CD28-induced T lymphocyte stimulation, in the presence (or absence) of IL-7, were studied in vitro. Small amounts of the drugs did not interfere with the capacity of IL-7 to stimulate T cell proliferation, but higher concentrations significantly decreased IL-7-induced T cell proliferation both in cells from HIV-infected patients and in cells from healthy donors. IL-7 is known to down-modulate its own receptor on the surface of CD4 and CD8 T lymphocytes in vitro. In CD4 lymphocytes from healthy donors or HIV-infected patients, neither AZT, nor saquinavir, nor a combination of the two, interfered with this property. In contrast, AZT + saquinavir worsened the IL-7-induced down-regulation of CD127 expression by CD8 T cells from HIV-infected patients, while no such effect was observed with CD8 T cells from healthy donors. Our data suggest that, under certain conditions, antiretroviral therapy could interfere with the expression and function of the IL-7/IL-7R system, and more particularly it may affect the CD8-lymphocyte compartment of HIV-infected patients.
Beq
Stéphanie
S
Unité d'Immunogénétique Cellulaire, Département de Médecine Moléculaire, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Bugault
Florence
F
Colle
Jean-Hervé
JH
Lambotte
Olivier
O
Delfraissy
Jean-François
JF
Thèze
Jacques
J
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D015851:Interleukin-7 / Q000502:physiology*; D053699:Interleukin-7 Receptor alpha Subunit / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D019258:Saquinavir / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology*
D017320:HIV Protease Inhibitors; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D020395:Receptors, Interleukin-7; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D019258:Saquinavir