SPECIFIC TH1 CYTOKINE DOWN-REGULATION ASSOCIATED WITH PRIMARY CLINICALLY DERIVED HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 NEF GENE-INDUCED EXPRESSION

HIV-1 infection is associated with a progressive and functional declin e in the CD4(+) lymphoid Th1 subset, Here, we propose that the HIV nef gene product may function as a specific regulator of Th1 cytokine pro duction, By use of a T cell-specific inducible expression system, we s how that upon T cell activation, induced nef expression down-regulated both IL-2 and IFN-gamma production in a dose-dependent manner, wherea s IL-4, IL-9, IL-13, IL-8, and TNF-alpha production remained unaffecte d, In addition to this, independent transfected clones expressing vari ous nef genes, including nef sequences amplified directly from an HIV- 1 primary clinical isolate, displayed a similar pattern of cytokine ex pression, The specific Th1 impairment induced by net; therefore, seems to be an important and conserved feature of HIV-1 infection and may r epresent a significant function of this viral gene in AIDS pathogenesi s.