Functional change of human peripheral blood monocyte-derived dendritic cells after recombinant adeno-associated virus type 2-mediated HBsAg gene infection.
OBJECTIVE
To observe the changes in the functions of human peripheral blood monocyte-derived dendritic cells (DCs) after hepatitis B virus surface antigen (HBsAg) gene infection mediated by recombinant adeno-associated virus type 2 (rAAV).


METHODS
The levels of both interleukin (IL)-12 in the supernatant of in vitro cultured DCs infected with rAAV-HbsAg and interferon gamma (IFN-gamma) in the supernatant of the lymphocyte populations co-cultured with DCs were determined by ELISA. The functions of the rAAV-HbsAg-infected DCs were assessed by mixed leukocyte reaction (MLR), and the changes of the surface markers (including CD80, CD83, CD86 and HLA-DR) in response to the infection were detected by flow cytometry.


RESULTS
After rAAV-HBsAg infection, the IL-12 secretion of DCs was significantly enhanced (P <0.05), while IFN-gamma production by the lymphocyte populations co-cultured with rAAV-HbsAg-infected DCs was reduced (P <0.01). rAAV-HBsAg infection of DCs did not affect the surface marker expressions and stimulation ability of the DCs in allogeneic lymphocytes reaction.


CONCLUSIONS
DCs infected by rAAV-HBsAg are more efficient than naive DCs in eliciting the differentiation of the lymphocytes toward T helper type I cells, but the functions and the surface markers of DCs remain unaffected after the infection, suggesting the applicability of rAAV as a potentially useful vector for HBsAg gene transfer into the DCs for HBV immunotherapy.
Hu
Gui-fang
GF
Department of Epidemiology, First Military Medical University, Guangzhou 510515, China. guifanghu@hotmail.com
Wu
Xiao-bing
XB
Yu
Shou-yi
SY
Kang
Yu
Y
Hou
Yun-de
YD
D003713:Dendritic Cells / Q000502:physiology*; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009000:Monocytes / Q000502:physiology*; D011995:Recombination, Genetic
D006514:Hepatitis B Surface Antigens; D018664:Interleukin-12; D007371:Interferon-gamma