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 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.


CONCLUSIONS
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.
Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria.
Wilfried
W
Posch
Sylvain
S
Cardinaud
Chiraz
C
Hamimi
Adam
A
Fletcher
Annelies
A
Mühlbacher
Klaus
K
Loacker
Paul
P
Eichberger
Manfred P
MP
Dierich
Gianfranco
G
Pancino
Cornelia
C
Lass-Flörl
Arnaud
A
Moris
Asier
A
Saez-Cirion
Doris
D
Wilflingseder
D000914:Antibodies, Viral / Q000276:immunology; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002999:Clone Cells; D003165:Complement System Proteins / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000914:Antibodies, Viral; D000956:Antigens, Viral; D007371:Interferon-gamma; D003165:Complement System Proteins