Author(s): Mao GY, Yang J, Chen HB, Guo W, Nie HX
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Abstract OBJECTIVE: To investigate the deficiency of the expression of the phenotypes (CD(1a), CD(83), CD(40), CD(86)) and cytokines (IL-12 and IL-10) by human peripheral blood monocyte (PBMC)-derived dendritic cell (DCs) from asthmatic subjects, and their influence on naive T cell polarization. METHODS: Adherent cells were isolated from peripheral blood samples in asthmatic patients and in healthy volunteers, and were cultured with granulocyte-macrophage colony-stimulating factor and IL-4 as immature DC (iDC). iDCs were stimulated with lipopolysaccharide as mature DC (mDCs). Nonadherent cells were obtained from umbilical cord blood by idem methods, and naïve T cells were sorted by adding anti-CD(4) and anti-CD(45RA) in nonadherent cells respectively and magnetic microbeads. Naïve T cells and mDCs from two groups were co-cultured in complete RPMI1640 media respectively, and naive T cells polarized as T helper cells 1 (Th1) and Th2. The expression of the CD(1a), CD(83), CD(40) and CD(86) on mature DCs were examined by fluorescent activated cell sorter. IL-12 and IL-10 released by mDCs and IL-4 and IFNgamma produced by Th cells were measured by ELISA. RESULTS: (1) The expression of CD(86) on dendritic cells from atopic asthmatics was higher than that from healthy control subjects (40.75 +/- 3.99 vs 29.88 +/- 1.25, P < 0.01). (2) The levels of IL-12, IL-12p40 and IL-10 produced by DCs from asthmatic subjects were all significantly lower than those from healthy control group (217.79 +/- 118.65 vs 905.66 +/- 495.32, P < 0.01; 2072.22 +/- 1496.37 vs 5569.43 +/- 2922.75, P < 0.01; 336.89 +/- 261.52 vs 1425.00 +/- 1148.87, P < 0.05, respectively). (3) IL-4 production by Th2 cells which were primed by DCs from asthmatics was significantly increased as compared to that from control group (368.56 +/- 190.72 vs 584.91 +/- 290.13, P < 0.01); On the contrary, IFNgamma in the patient group was reduced as compared to that in the control group (425.33 +/- 164.94 vs 49.86 +/- 18.14, P < 0.05). (4) In the patient group, the level of IL-12 was positively correlated to that of IFNgamma (P < 0.05), negatively correlated to that of IL-4 (P < 0.05); IL-10 was negatively correlated to IL-4 (P < 0.05). (5) There was a positive correlation between IL-12 and IL-10 in the two groups (P < 0.01). CONCLUSION: Because of DC deficiency, naïve T cells preferentially polarize to Th2 which synthesize more Th2-type cytokine (i.e. IL-4) and T cell tolerance cannot be induced, which may be one of the important pathogenic mechanisms for allergic asthma.
This article was published in Zhonghua Nei Ke Za Zhi
and referenced in Immunochemistry & Immunopathology