HIV type 1 Tat protein inhibits interleukin 12 production by human peripheral blood mononuclear cells.
HIV-1 Tat protein, which trans-activates HIV-1 expression, exerts many effects on host immune function. Meanwhile, PBMCs and pulmonary macrophages from HIV-1-infected patients produce only a small amount of IL-12, which plays an essential role in the development of helper T type 1 (Th1) cells, and in the generation of cytotoxic T lymphocytes. We examined the possibility that Tat suppresses IL-12 production by PBMCs from healthy donors. Tat significantly inhibited IL-12 production by human PBMCs stimulated with Staphylococcus aureus Cowan 1 strain (SAC) at concentrations between 5 and 40 ng/ml. Immunoabsorption by using polyclonal antibody to Tat abolished the suppression of the IL-12 production by Tat. Tat at the same concentrations did not affect IL-10, IL-6, or TNF-alpha production. Other HIV-1 proteins (Nef and gp120) did not influence IL-12 production. Tat also suppressed the expression of mRNA encoding the p40 chain of IL-12, whereas it did not affect the expression of mRNA encoding IL-10 and beta-actin. IL-12 production by monocytes, separated from PBMCs by the adhesion method, was also inhibited by Tat. These results suggest that Tat protein is one of the main causes of decreased IL-12 production by PBMCs (mostly by monocytes) from HIV-1-infected individuals.
Department of Microbiology, Yamanashi Medical University, Tamahocho, Japan.
M
M
Ito
T
T
Ishida
L
L
He
F
F
Tanabe
Y
Y
Rongge
Y
Y
Miyakawa
H
H
Terunuma
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D015693:Gene Products, nef / Q000378:metabolism / Q000494:pharmacology; D015696:Gene Products, tat / Q000378:metabolism* / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism / Q000494:pharmacology; D015497:HIV-1 / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D054311:nef Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D015696:Gene Products, tat; D015699:HIV Envelope Protein gp120; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D054311:nef Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D016753:Interleukin-10; D018664:Interleukin-12