Contributions
Abstract: EP1581
Type: ePoster
Abstract Category: RIMS - Neurobiology & Rehabilitation
The CNS has been traditionally viewed as a (partially) immune-privileged site, although there is noteworthy literature on rejection of allogeneic grafts from the brain. With the advent of cell therapy, different cellular platforms are emerging, including autologous cells produced individually for each patient, versus allogeneic cell platforms, which may be distributed as a shelf product. Therefore, it is important to determine the need for immunosuppressive treatment to prevent rejection of allogeneic cellular therapies.
Neural stem cells (NSC) possess powerful immune-regulatory properties, which inhibit antigen presenting cells and T cell activation and proliferation. While these properties may protect transplanted NSCs, we have recently shown that allogeneic NSC grafts survive in a quiescent, non-functional state; they lose with time their immune-regulatory functions and are rejected from the naïve brain. We found that expression of green-fluorescent-protein (GFP) provokes an especially strong immune response and rejection.
We examined here whether there are differences between various brain regions in eliciting an immune response and rejecting grafts of highly immunogenic GFP+ allogeneic stem/precursor cells. These grafts were rejected efficiently from the mouse Striatum but persisted in the Hippocampus and ventricles. IBA-1+ microglia/macrophages and CD3+ T cells heavily infiltrated the striatal grafts. In comparison, hippocampal grafts exhibited milder infiltration of IBA-1+ cells, and T cells did not penetrate them efficiently, but accumulated in their periphery.
We then examined the role of CD200, a major immune-inhibitory signal, limiting various inflammatory processes, in this brain region-specific immune privilege property. While NSC expressed CD200 prior to transplantation, its expression was lost within 2 days post striatal transplantation, but persisted at least 2 months in hippocampal grafts. Loss of CD200 expression in extra-hippocampal portions of the graft was associated with a strong local IBA-1+ and CD3+ cell infiltration into the graft. Furthermore, Astrocytes, which do not normally express CD200, were rejected efficiently from the Hippocampus.
In conclusion, the Hippocampus (and CSF) is a partially immune-privileged site for transplanted stem cell grafts that possess immune-regulatory properties. The Hippocampus induces continued expression of CD200 on transplanted NSCs to protect them from the allogeneic immune response and rejection.
Disclosure:
Tamir Ben-Hur: Scientific advisory board member of Kadimastem, Mapi Pharma, Regenera Pharma, Stem Cell Medicine
Nina Fainstein: nothing to disclose
Supported by The Judy and Sidney Swartz Foundation and The Taubman Foundation.
Abstract: EP1581
Type: ePoster
Abstract Category: RIMS - Neurobiology & Rehabilitation
The CNS has been traditionally viewed as a (partially) immune-privileged site, although there is noteworthy literature on rejection of allogeneic grafts from the brain. With the advent of cell therapy, different cellular platforms are emerging, including autologous cells produced individually for each patient, versus allogeneic cell platforms, which may be distributed as a shelf product. Therefore, it is important to determine the need for immunosuppressive treatment to prevent rejection of allogeneic cellular therapies.
Neural stem cells (NSC) possess powerful immune-regulatory properties, which inhibit antigen presenting cells and T cell activation and proliferation. While these properties may protect transplanted NSCs, we have recently shown that allogeneic NSC grafts survive in a quiescent, non-functional state; they lose with time their immune-regulatory functions and are rejected from the naïve brain. We found that expression of green-fluorescent-protein (GFP) provokes an especially strong immune response and rejection.
We examined here whether there are differences between various brain regions in eliciting an immune response and rejecting grafts of highly immunogenic GFP+ allogeneic stem/precursor cells. These grafts were rejected efficiently from the mouse Striatum but persisted in the Hippocampus and ventricles. IBA-1+ microglia/macrophages and CD3+ T cells heavily infiltrated the striatal grafts. In comparison, hippocampal grafts exhibited milder infiltration of IBA-1+ cells, and T cells did not penetrate them efficiently, but accumulated in their periphery.
We then examined the role of CD200, a major immune-inhibitory signal, limiting various inflammatory processes, in this brain region-specific immune privilege property. While NSC expressed CD200 prior to transplantation, its expression was lost within 2 days post striatal transplantation, but persisted at least 2 months in hippocampal grafts. Loss of CD200 expression in extra-hippocampal portions of the graft was associated with a strong local IBA-1+ and CD3+ cell infiltration into the graft. Furthermore, Astrocytes, which do not normally express CD200, were rejected efficiently from the Hippocampus.
In conclusion, the Hippocampus (and CSF) is a partially immune-privileged site for transplanted stem cell grafts that possess immune-regulatory properties. The Hippocampus induces continued expression of CD200 on transplanted NSCs to protect them from the allogeneic immune response and rejection.
Disclosure:
Tamir Ben-Hur: Scientific advisory board member of Kadimastem, Mapi Pharma, Regenera Pharma, Stem Cell Medicine
Nina Fainstein: nothing to disclose
Supported by The Judy and Sidney Swartz Foundation and The Taubman Foundation.