Abrogation of in vitro suppression of human immunodeficiency virus type 1 (HIV-1) replication mediated by CD8+ T lymphocytes of asymptomatic HIV-1 carriers by staphylococcal enterotoxin B and phorbol esters through induction of tumor necrosis factor alpha.
CD8+ T lymphocytes of asymptomatic human immunodeficiency virus type 1 (HIV-1) carriers (AC) suppress HIV-1 replication in vitro. Failure of host defense mechanisms and increased virus proliferation are associated with disease progression. The exact mechanisms inducing these changes at the advanced stage of the disease are still obscure. In this study, we searched for experimental conditions favoring the abrogation of the suppression of viral replication in peripheral blood mononuclear cells (PBMC) of AC by using various pharmacological and biological probes modifying cell activation. Among such agents, staphylococcal enterotoxin B (SEB) and phorbol 12-myristate 13-acetate (PMA) markedly increased otherwise low levels of HIV-1 replication in cultures of phytohemagglutinin-stimulated AC PBMC following in vitro HIV-1 LAI infection. A similar but less pronounced virus induction was also observed in macrophage-tropic HIV-1. Individual pretreatment of CD4+ and CD8+ PBMC fractions with these agents caused a reduction in CD8+ cell proliferation and enhanced HIV-1 replication in CD4+ cells. SEB- and PMA-mediated augmentation of HIV-1 replication in AC PBMC was significantly blocked by neutralizing antibody to tumor necrosis factor-alpha (TNF-alpha), although recombinant TNF-alpha alone failed to reproduce the effects of SEB or PMA. Our results suggest that the induction of TNF-alpha may be one of the mechanisms that overcomes the CD8+-induced suppression of HIV-1 replication in AC and that it may induce HIV-1 replication.
Kubo
M
M
Department of Immunotherapeutics, Tokyo Medical and Dental University, Japan.
Ohashi
T
T
Fujii
M
M
Oka
S
S
Iwamoto
A
A
Harada
S
S
Kannagi
M
M
D000906:Antibodies / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004768:Enterotoxins / Q000494:pharmacology*; D016655:HIV Core Protein p24 / Q000032:analysis / Q000096:biosynthesis; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000821:virology; D013211:Staphylococcus aureus; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
D000906:Antibodies; D016207:Cytokines; D004768:Enterotoxins; D016655:HIV Core Protein p24; D014409:Tumor Necrosis Factor-alpha; C031818:enterotoxin B, staphylococcal; D013755:Tetradecanoylphorbol Acetate