Activated B lymphocytes from human immunodeficiency virus-infected individuals induce virus expression in infected T cells and a promonocytic cell line, U1.
Freshly isolated B lymphocytes from patients infected with human immunodeficiency virus (HIV), in contrast to B cells from normal controls, were shown to induce viral expression in two cell lines: ACH-2, a T cell line, and U1, a promonocytic cell line, which are chronically infected with HIV, as well as in autologous T cells. In 10 out of 10 HIV-infected individuals with hypergammaglobulinemia, spontaneous HIV-inductive capacity was found with highly purified peripheral blood B cells, whereas peripheral blood or tonsillar B cells from six healthy, HIV-negative donors did not induce HIV expression unless the cells were stimulated in vitro. The induction of HIV expression was observed in direct coculture experiments of B lymphocytes and HIV-infected cells, and could also be mediated by supernatants from cultures of B cells. Significantly higher amounts of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) were detected in the B cell culture supernatants from HIV-infected patients with hypergammaglobulinemia (IL-6: mean = 536 pg/ml; TNF-alpha: mean = 493 pg/ml), as compared with normal uninfected controls (IL-6: mean = 18 pg/ml; TNF-alpha: mean = 23 pg/ml). Antibodies against these cytokines abolished the HIV-inductive capacity of B cells. We conclude that in vivo activated B cells in HIV-infected individuals can upregulate the expression of virus in infected cells by secreting cytokines such as TNF-alpha and IL-6, and, therefore, may play a role in the progression of HIV infection.
Rieckmann
P
P
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Poli
G
G
Kehrl
J H
JH
Fauci
A S
AS
D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D015658:HIV Infections / Q000276:immunology* / Q000382:microbiology; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation; D009000:Monocytes / Q000382:microbiology*; D013601:T-Lymphocytes / Q000382:microbiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014775:Virus Activation / Q000276:immunology
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha