HIV-1 Nef protein inhibits the in vitro induction of a specific antibody response to Candida albicans by an early up-regulation of IL-15 production.
We have previously demonstrated that exogenous Nef protein induced activation of normal human T cells up-regulating IL-15 production by monocytes. Since HIV-1 infection results in the early impairment of immune functions we decided to evaluate if Nef is able to modulate the induction of a specific antibody response. Human peripheral blood mononuclear cells from healthy donors were induced in vitro to mount a specific antibody response to the Candida albicans antigen. We show that Nef inhibited, in a dose-dependent manner, the induction of the anti-C. albicans antibody response. The ability of an anti-Nef antibody to prevent such inhibition indicates that the effect was indeed Nef-specific. In the Nef-treated cultures an early increase of IL-15 production was observed and the addition of anti-IL-15 antibody abrogated the Nef-induced inhibitory effect. Moreover the addition of IL-15 to the cultures inhibited, as well as Nef, the induction of the specific antibody response. Thus, our results suggest that Nef may inhibit the induction of a specific antibody response by an early up-regulation of IL-15 production. A better comprehension of this phenomenon may be important for unravelling some aspects of the B cell defects in HIV infection.
Giordani
L
L
Department of Immunology, Istituto Superiore di Sanità, Rome, Italy.
Giacomini
E
E
Quaranta
M G
MG
Viora
M
M
D000908:Antibodies, Fungal / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology*; D002478:Cells, Cultured; D015693:Gene Products, nef / Q000276:immunology* / Q000502:physiology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D015854:Up-Regulation; D054311:nef Gene Products, Human Immunodeficiency Virus
D000908:Antibodies, Fungal; D015693:Gene Products, nef; D019409:Interleukin-15; D054311:nef Gene Products, Human Immunodeficiency Virus