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

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• 作者：Wilfried Posch ; PhD^a ; Sylvain Cardinaud ; PhD^b ; Chiraz Hamimi ; MSc^c ; Adam Fletcher ; PhD^d ; Annelies Mü ; hlbacher ; MD^e ; Klaus Loacker ; PhD^e ; Paul Eichberger ; PhD^f ; Manfred P. Dierich ; MD^a ; Gianfranco Pancino ; MD ; PhD^c ; Cornelia Lass-Flö ; rl ; MD^a ; Arnaud Moris ; PhD^b ; Asier Saez-Cirion ; PhD^c ; Doris Wilflingseder ; PhD^a ; ^{doris.wilflingseder@i-med.ac.at}
• 关键词：HIV ; IgG ; opsonization ; dendritic cells ; cytotoxic T lymphocytes
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2012
• 出版时间：December, 2012
• 年：2012
• 卷：130
• 期：6
• 页码：1368-1374.e2
• 全文大小：604 K

文摘

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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-¦Ã 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.