VITD3 ile hematopoetik kök hücre türevli tolorejenik DC üretimi

Dendritic cells (DCs) are main activator and regulator cells in immune response due to their bridging function between the innate and adaptive immune system. Upon ingestion of antigens from peripheral tissues in response the triggering of an immune response, DCs migrate to lymph node to activate antigen specific T cells. It is a well-known fact that DCs are the most important antigen presenting cells for the T cell stimulation, a phenomenon that allows them to be utilised as therapeutic agents against cancer and chronic infections. Besides that DCs have been used for immune suppression against autoimmune diseases, including multiple sclerosis (MS), atherosclerosis, psoriasis etc. DCs are considered as a heterogeneous cell population mainly due to their cell surface receptors such as classical DCs (cDCs), plasmacytoid DCs (pDCs) and monocyte derived DCs (moDCs). Each DC has different properties under inflammation conditions depending on their surface receptors and cytokine secretions. moDCs have been used as a therapeutic vaccine to suppress autoimmune reactions after treatment with immune suppressive molecules such as, corticosteroids, cyclosporine (CsA), prostaglandin E2, VitD3, rapamycin etc. Other DCs especially cDCs may be used as antigen specific immune suppressive DC vaccine based on their T cell interaction and stimulation capacity which is known to be better than that for moDCs. In this thesis, tolerogenic DCs (tol-DC) were differentiated from hematopoietic stem cells using stimulatory agents such as Flt-3L, GM-CSF, SCF, IL-4, and VitD3. Then tol-DCs were co-cultured with T lymphocytes to examine their tolerogenic properties on cell mediated immune system. To our knowledge this study is one of the first examples to demonstrate VitD3 induced tol-DCs generation from HSC while negatively affecting DC generation. Although, tol-DCs have decreased HLA-DR expression which means that the presentation capacity of DCs are also decreased, they present an increase CD86 expression that may causes inhibition of T lymphocytes based on the interaction between CTLA-4 rather than CD28. Strikingly, their T cell stimulation capacity and induction of anti-tumor response are lower than control DCs. Overall findings of this study suggest that HSC derived tol-DCs may be an alternative way to prepare tol-DC vaccines.