Role of tumour necrosis factor-alpha (TNF-alpha) in the induction of HIV-1 gp120-mediated CD4+ T cell anergy.
The HIV-1 envelope glycoprotein (gp 120) is known to induce antigen-specific and non-specific CD4+ T cell anergy. We found that early T cell activation, as indicated by HLA-DP expression in the early G1 (G1A) phase of the cell cycle, and the inhibition of mitogen-mediated IL-2 production induced by gp120, required TNF-alpha produced by gp120-stimulated macrophages. In the presence of an antibody to TNF-alpha, these changes induced by gp120 were inhibited, while recombinant TNF-alpha induced similar abnormalities of CD4+ T cells, even in the absence of gp120. On the other hand, inhibition of the mixed lymphocyte reaction (MLR) in CD4+ T cells by gp120, which may be related to gp120-mediated down-regulation of CD4 expression on T cells and activation of protein tyrosine kinase p56(lck) in CD4+ T cells, was observed even in the absence of macrophage-derived TNF-alpha induced by gp120. These observations indicate that both TNF-alpha-dependent and independent events contribute to gp120-mediated CD4+ T cell anergy, and TNF-alpha appears to play an important role in inducing CD4+ T cell anergy in HIV-1 infection.
Kaneko
H
H
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
Hishikawa
T
T
Sekigawa
I
I
Hashimoto
H
H
Okumura
K
K
Kaneko
Y
Y
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D017635:Clonal Anergy; D015536:Down-Regulation; D005434:Flow Cytometry; D016193:G1 Phase / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006682:HLA-DP Antigens / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008934:Mitogens / Q000276:immunology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000494:pharmacology
D015699:HIV Envelope Protein gp120; D006682:HLA-DP Antigens; D007376:Interleukin-2; D015850:Interleukin-6; D008934:Mitogens; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases