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Clinical and Diagnostic Laboratory Immunology, March 2005, p. 453-464, Vol. 12, No. 3
1071-412X/05/$08.00+0     doi:10.1128/CDLI.12.3.453-464.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Impaired Accessory Cell Function in a Human Dendritic Cell Line after Human Immunodeficiency Virus Infection

Division of Clinical Immunology, Mount Sinai School of Medicine, New York, New York¹

Received 20 July 2004/ Returned for modification 13 October 2004/ Accepted 28 December 2004

We generated human dendritic cell (DC) hybridoma cell lines by fusing HGPRT-deficient promonocytic U937 cells with immature DCs obtained by culturing peripheral blood monocytes with interleukin-4 (IL-4; 1,000 U/ml) and granulocyte-macrophage colony-stimulating factor (100 U/ml) for 7 days and mature DCs by treatment with tumor necrosis factor alpha (12.5 µg/ml) for 3 days. Only one fusion with immature DCs was successful and yielded four cell lines—HB-1, HB-2, HB-3, and HB-9—with an overall fusion efficiency of 0.0015%. The cell lines were stable in long-term culture, displayed morphological features typical of DCs, and expressed distinct class I and class II molecules not present on U937 (A*031012, B*51011, Cw*0701, DRB3*01011 52, and DR5*01011). A representative cell line, HB-2, that expressed DC markers including CD83, CD80 and CD86 could be induced to produce IL-12 through CD40 stimulation. After human immunodeficiency virus (HIV) infection, there was impairment of antigen-presenting cell (APC) function, which was manifested by an inability to stimulate allogeneic T-cell responses. There was no change in expression of major histocompatibility complex class I and class II antigens, CD83, CD40, CD4, CD11c, CD80, CD86, CD54, and CD58, or IL-12 production in the HIV-infected HB-2 cells. The HIV-infected HB-2 cells induced T-cell apoptosis in the cocultures. T-cell proliferation could be partially restored by using ddI, indinivir, and blocking anti-gp120 and anti-IL-10 antibodies. Our data suggest that there are multiple mechanisms that DCs use to inhibit T-cell responses in HIV-infected patients. The HB-2 cell line could be a useful model system to study APC function in HIV-infected DCs.