Antibodies attenuate the capacity of dendritic cells to stimulate HIV-specific cytotoxic T lymphocytes

Background Control of HIV is suggested to depend on potent effector functions of the virus-specific CD8+ T-cell response. Antigen opsonization can modulate the capture of antigen, its presentation, and the priming of specific CD8+ T-cell responses. Objective We have previously shown that opsonizatio...

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Published in:Journal of allergy and clinical immunology 2012-12, Vol.130 (6), p.1368-1374.e2
Main Authors: Posch, Wilfried, PhD, Cardinaud, Sylvain, PhD, Hamimi, Chiraz, MSc, Fletcher, Adam, PhD, Mühlbacher, Annelies, MD, Loacker, Klaus, PhD, Eichberger, Paul, PhD, Dierich, Manfred P., MD, Pancino, Gianfranco, MD, PhD, Lass-Flörl, Cornelia, MD, Moris, Arnaud, PhD, Saez-Cirion, Asier, PhD, Wilflingseder, Doris, PhD
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
Adjuvants
AIDS
Allergy and Immunology
Antibodies, Viral - immunology
Antigen Presentation
Antigens, Viral - immunology
Antiviral activity
Biological and medical sciences
Blood & organ donations
CD4 antigen
CD4-Positive T-Lymphocytes - immunology
CD8 antigen
Cell Proliferation
Clone Cells
Cloning
Coats
Complement activation
Complement System Proteins - immunology
cytotoxic T lymphocytes
Cytotoxicity
Dendritic cells
Dendritic Cells - immunology
Experiments
Fundamental and applied biological sciences. Psychology
Fundamental immunology
HIV
HIV - immunology
HIV Infections - immunology
Human immunodeficiency virus
Human viral diseases
Humans
IgG
Immunodeficiencies
Immunodeficiencies. Immunoglobulinopathies
Immunoglobulin G
Immunology
Immunopathology
Infectious diseases
Interferon-gamma - immunology
Life Sciences
Lymphocyte Activation
Lymphocytes
Lymphocytes T
Medical sciences
Opsonization
Plasma
Retrovirus
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
T-Lymphocytes, Cytotoxic - immunology
Vaccines
Viral diseases
Viral diseases of the lymphoid tissue and the blood. Aids
Viral infections
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Summary:Background Control of HIV is suggested to depend on potent effector functions of the virus-specific CD8+ T-cell response. Antigen opsonization can modulate the capture of antigen, its presentation, and the priming of specific CD8+ T-cell responses. Objective We have previously shown that opsonization of retroviruses acts as an endogenous adjuvant for dendritic cell (DC)–mediated induction of specific cytotoxic T lymphocytes (CTLs). However, in some HIV-positive subjects, high levels of antibodies and low levels of complement fragments coat the HIV surface. Methods Therefore we analyzed the effect of IgG opsonization on the antigen-presenting capacity of DCs by using CD8+ T-cell proliferation assays after repeated prime boosting, by measuring the antiviral activity against HIV-infected autologous CD4+ T cells, and by determining IFN-γ secretion from HIV-specific CTL clones. Results We find that DCs exposed to IgG-opsonized HIV significantly decreased the HIV-specific CD8+ T-cell response compared with the earlier described efficient CD8+ T-cell activation induced by DCs loaded with complement-opsonized HIV. DCs exposed to HIV bearing high surface IgG levels after incubation in plasma from HIV-infected subjects acted as weak stimulators for HIV-specific CTL clones. In contrast, HIV opsonized with plasma from patients exhibiting high complement and low IgG deposition on the viral surface favored significantly higher activation of HIV-specific CD8+ T-cell clones. Conclusion Our ex vivo and in vitro observations provide the first evidence that IgG opsonization of HIV is associated with a decreased CTL-stimulatory capacity of DCs.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2012.08.025