In Type 1 Diabetes (T1D), the use of recombinant insulin to maintain normoglycemia does not address the underlying cause of the disease, T cell mediated Î² cell destruction. T1D dendritic cell (DC) therapy addresses this issue by promoting Î² cell specific self-tolerance via modification of the T cell response. The use of DC to circumvent T1D progression and promote Î² cell self-tolerance was first investigated approximately 2 decades ago. DC from the pancreatic draining lymph nodes of non-obese diabetic (NOD) mice prevented the onset of T1D when adoptively transferred to NOD mice at an early stage of the disease. Since that time numerous studies have investigated the effectiveness of bone marrow derived dendritic cells (BM-DC) in preventing T1D in NOD mice.
Feili-Hariri et al. utilized GM-CSF and IL-4 to expand DC from bone marrow precursor cells ex vivo and demonstrated their ability to effectively prevent T1D onset. These and other investigations have revealed that GM-CSF/IL-4 BM-DC treatment initiates a protective Th2 response. Furthermore, evidence suggests that the expression of co-stimulatory molecules and production of TGFÎ² are related to the ability of BM-DC to elicit immunoregulatory responses and inhibit autoimmune disease. Though this evidence supports the use of BM-DC to prevent T1D, more work is needed to validate the strategy prior to translation into the clinic. In particular, evidence suggests that various BM-DC culture conditions may have differing effects on the phenotype of the DC and, as a consequence, their ability to protect from T1D.
Chang-Qing Xia, Characterization of Bone Marrow-Derived Dendritic Cells Developed in Serum-Free Media and their Ability to Prevent Type 1 Diabetes in Nonobese Diabetic Mice
Last date updated on July, 2014