[Experimental study of CTLA4Ig gene-modified dendritic cells transfused neonatally inducing asthmatic immune tolerance in adult mice].
OBJECTIVE
To explore the effects of CTLA4Ig gene-modified dendritic cells on the mechanism of immune regulation in asthma with Th2 superiority.


METHODS
Newborn BALB/c mice are randomly divided into 2 groups of AdCTLA4Ig-DC intervention and AdGFP modified dendritic cells (AdGFP-DC) intervention by randomization (n = 10 each). CTLA4Ig gene-modified dendritic cells (AdCTLA4Ig-DC) and AdGFP-DC were infused separately. Newborn BALB/c mice in both groups were fed for 6 - 8 weeks. Additional 6 - 8 weeks BALB/c mice were randomly divided into 2 groups of control and asthma (n = 10 each). The saline-sensitized/challenged mice received an intraperitoneal injection while inhalation was administered in the control group. Ovalbumin (OVA) was used similarly in the remaining three groups. The manifestations of OVA challenged mice in each group, bronchoalveolar lavage fluid (BALF) eosinophils and pathological changes in airway were observed to examine the effects of CTLA4Ig gene-modified dendritic cells on airway inflammation. The levels of IgE, Interleukin (IL)-4, IL-10 and IFN-γ were detected by enzyme-linked immunosorbent assay (ELISA).


RESULTS
Rapid respiration and pulmonary inflammatory infiltration were obvious in the asthma group. CTLA4Ig gene-modified dendritic cells transfused neonatally significantly improved the symptoms of asthma in adulthood and reduced the infiltration of inflammatory cells in bronchial submucosa. The levels of IgE and IL-4 in serum and BALF in the AdCTLA4Ig-DC intervention group were significantly lower than those in the asthma group (IgE: (3.9 ± 1.3)× 10(5) pg/ml vs (5.3 ± 1.7)× 10(5) pg/ml and (22.9 ± 11.8)× 10(3) pg/ml vs (122.0 ± 59.6)× 10(3) pg/ml, IL-4: (70.5 ± 7.0) pg/ml vs (88.7 ± 9.2) pg/ml and (46.9 ± 2.9) pg/ml vs (73.3 ± 8.7) pg/ml, all P < 0.05). The levels of IL-10 in serum and BALF in the AdCTLA4Ig-DC intervention group were significantly higher than those in the asthma group ((442 ± 8) pg/ml vs (227 ± 11) pg/ml, (83 ± 42) pg/ml vs (27 ± 11) pg/ml, both P < 0.05). The levels of IFN-γ in serum and BALF in AdCTLA4Ig-DC intervention group showed no significant difference with those in the asthma group (both P > 0.05). The eosinophil level in BALF was significantly lower than that in the asthma group ((18.5 ± 1.9)× 10(4)/ml vs (62.3 ± 6.7)× 10(4)/ml, P < 0.05).


CONCLUSIONS
CTLA4Ig gene-modified dendritic cells transfused neonatally may reduce the secretion of Th2 cytokines in OVA-sensitized/challenged adult mice. The expression of CTLA4Ig gene induces immune tolerance in asthma.
Department of Respiratory Disease, Children's Hospital of Fudan University, Shanghai 201102, China.
Jin
J
Zhang
Chao
C
Chen
Yan
Y
Chen
Li-bo
LB
Wang
Xiao-bo
XB
Zhang
Ming-zhi
MZ
Zhang
D000069594:Abatacept; D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D001249:Asthma / Q000276:immunology* / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007108:Immune Tolerance; D018796:Immunoconjugates / Q000235:genetics / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D011897:Random Allocation
D018796:Immunoconjugates; D000069594:Abatacept