![]() Allogeneic MHC molecules can be shed into the environment where they are processed and presented to lymphocytes by APCs. Expansion of MHC-specific CD4 + T cells can be detected using an ex-vivo MLR. IL-4 secretion by T cells restimulated with donor allogeneic MHC II molecules can be measured by ELISPOT. Allogeneic MHC II molecules are directly recognized by alloreactive CD4 + T cells, which induces secretion of IL-4 or IFN-γ and clonal expansion of helper T cells. Effector function of cytotoxic T cells specific for donor allogeneic MHC I molecules can be measured using cytotoxicity assays. IFN-γ secretion by T cells restimulated with donor allogeneic MHC I molecules can be measured using an ELISPOT. Following injection of MHC-mismatched MSCs in vivo, allogeneic MHC I molecules are directly recognized by alloreactive CD8 + T cells, which induces secretion of interferon (IFN)-γ and clonal expansion of cytotoxic T cells. In-vivo immune responses to MHC-mismatched MSCs and corresponding assays. This review details what is currently known about the immunogenicity of allogeneic MSCs and suggests contemporary assays that could be utilized in future studies to appropriately identify and measure immune responses to MHC-mismatched MSCs.Īllogeneic Cytotoxicity ELISPOT Immunogenicity Major histocompatibility complex Mesenchymal stem cell Microcytotoxicity Mixed leukocyte reaction. Pre-clinical and clinical studies that document the MHC haplotype of donors and recipients and measure immune responses following MSC treatment are necessary to answer this critical question. The clinical implications of immune responses to MHC-mismatched MSCs are still unknown. Studies that control for MHC expression have reported both cell-mediated and humoral immune responses to MHC-mismatched MSCs. The prevailing dogma has been that allogeneic MSCs are immune privileged, but there have been very few studies that control for matched or mismatched major histocompatibility complex (MHC) molecule expression and that examine immunogenicity in vivo. Allogeneic MSCs are especially attractive due to their potential to provide immediate care at the time of tissue injury or disease diagnosis. Autologous and allogeneic adult mesenchymal stem/stromal cells (MSCs) are increasingly being investigated for treating a wide range of clinical diseases.
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