OBJECTIVES: A comparative immunological evaluation of multiple sclerosis (MS) patients receiving IFNbeta treatment and patients who are not receiving treatment may help clarify IFNbeta neurological mechanisms and lead the way to an effective dendritic cell (DC) immunotherapy. This type of study helps clarify the pathological function of T cells and DCs within the TH1/TH2/TH3 network as well as the specific interactions between TH1/TH2/TH3 cytokines implicated in MS pathological mechanisms and determine the best way of reestablishing the TH1/TH2/TH3 network equilibrium. METHODS: We studied network interactions between TH1/TH2/TH3 cytokine levels in serum and supernatants of whole blood and CD14+ monocyte-derived DCs in the remission phase of the disease and in correlation to the Expanded Disability Status Scale (EDSS). RESULTS: We found that TH1 dysregulation results in a disruption of the maturation and activation of dendritic and T cells, and a lack of T-regulating cells for the induction of self-tolerance; IFNbeta mechanisms restore regulation by reestablishing the network balance but fail to resolve the disease completely due to in vivo IL12p70 network interactions leading to the deletion of self-aggressive cells. CONCLUSIONS: Our results indicate that a specific DC immunotherapy could cure rather than treat MS. The best point to reestablish the normal physiological cycle is at the immature DC stage which can be done in vitro with treated peripheral blood CD14+ cells and used in vivo to stimulate the expansion of specific regulatory T cells.
OBJECTIVES: A comparative immunological evaluation of multiple sclerosis (MS) patients receiving IFNbeta treatment and patients who are not receiving treatment may help clarify IFNbeta neurological mechanisms and lead the way to an effective dendritic cell (DC) immunotherapy. This type of study helps clarify the pathological function of T cells and DCs within the TH1/TH2/TH3 network as well as the specific interactions between TH1/TH2/TH3 cytokines implicated in MS pathological mechanisms and determine the best way of reestablishing the TH1/TH2/TH3 network equilibrium. METHODS: We studied network interactions between TH1/TH2/TH3 cytokine levels in serum and supernatants of whole blood and CD14+ monocyte-derived DCs in the remission phase of the disease and in correlation to the Expanded Disability Status Scale (EDSS). RESULTS: We found that TH1 dysregulation results in a disruption of the maturation and activation of dendritic and T cells, and a lack of T-regulating cells for the induction of self-tolerance; IFNbeta mechanisms restore regulation by reestablishing the network balance but fail to resolve the disease completely due to in vivo IL12p70 network interactions leading to the deletion of self-aggressive cells. CONCLUSIONS: Our results indicate that a specific DC immunotherapy could cure rather than treat MS. The best point to reestablish the normal physiological cycle is at the immature DC stage which can be done in vitro with treated peripheral blood CD14+ cells and used in vivo to stimulate the expansion of specific regulatory T cells.
Authors: Alla L Zozulya; Benjamin D Clarkson; Sonja Ortler; Zsuzsanna Fabry; Heinz Wiendl Journal: J Mol Med (Berl) Date: 2010-03-09 Impact factor: 4.599