AEGiS-07IAC: The role of IL-6 and TNF-alpha production by B-lymphocytes in HIV infection.

7th International AIDS Conference

Florence, Italy — June 16-21, 1991

The role of IL-6 and TNF-alpha production by B-lymphocytes in HIV infection.

Int Conf AIDS 1991 Jun 16-21; 7:26 (abstract no. M.A.19)
Rieckmann P, Poli G, Fox CH, Kehrl JH, Fauci AS; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

OBJECTIVE: To investigate the role of IL-6 and TNF-alpha produced by activated B cells in HIV infected individuals for their potential to support B cell activation and HIV expression.

METHODS: B cells were isolated from the blood or lymph node, cultured in the presence or absence of polyclonal B cell activators or recombinant gp120. TNF-alpha, IL-6 and immunoglobulin (Ig) production in the culture supernatants was measured using specific ELISAs. The HIV inductive capacity of cytokines released by activated B cells was tested in a direct coculture with chronically HIV infected T cell (ACH-2) or promonocytic (U1) or autologous infected T cells and virus release was measured by RT or p24 antigen assays. In situ hybridization was performed to detect virus expression in the lymph nodes.

RESULTS: Both cytokines were spontaneously secreted by B cells from HIV infected patients and could further be induced with gp120, whereas gp120 had no effect on B cells from seronegative donors in which IL-6 and TNF-alpha production was stimulated only with polyclonal B cell activators. Both cytokines were shown to be involved in the spontaneous in vitro lg production by B cells from HIV infected patients. The specific effect of gp120 on B cells is independent of CD4 or Fc receptors. A correlation was found between the expression of virus in germinal centers of lymph nodes and the spontaneous capacity of B cells to secrete IL-6 and TNF-alpha. p24 antigen release in autologous coculture experiments of B and T cells from HIV infected individuals was dependent on the presence of activated B cells.

CONCLUSIONS: Spontaneous and specifically (gp120) induced cytokine release by activated B cells from HIV infected individuals is important for the induction of HIV expression and may contribute to the high lg levels found in many patients.

Keywords: AEGIS, Interleukin-6, HIV Infections, Tumor Necrosis Factor, B-Lymphocytes, HIV, T-Lymphocytes, Cytokines, HIV Envelope Protein gp120, Antigens, CD, Antigens, CD4, HIV Envelope Protein gp160, Receptors, Fc, HIV Antigens, HIV Core Protein p24, CD9 antigen, In Vitro, Human, ICA7
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