Cryopreserved vitamin D3-tolerogenic dendritic cells pulsed with autoantigens as a potential therapy for multiple sclerosis patients

Altres ajuts: Cost Action BM1305BACKGROUND: Tolerogenic dendritic cells (tolDC) have been postulated as a potent immunoregulatory therapy for autoimmune diseases such as multiple sclerosis (MS). In a previous study, we demonstrated that the administration of antigen-specific vitamin D3 (vitD3) tolDC in mice showing clinical signs of experimental autoimmune encephalomyelitis (EAE; the animal model of MS) resulted in abrogation of disease progression. With the purpose to translate this beneficial therapy to the clinics, we have investigated the effectivity of vitD3-frozen antigen-specific tolDC pulsed with myelin oligodendrocyte glycoprotein 40-55 peptide (f-tolDC-MOG) since it would reduce the cost, functional variability and number of leukapheresis to perform to the patients. METHODS: Mice showing EAE clinical signs were treated with repetitive doses of f-tolDC-MOG. Tolerogenic mechanisms induced by the therapy were analysed by flow cytometry and T cell proliferation assays. RESULTS: Treatment with f-tolDC-MOG was effective in ameliorating clinical signs of mice with EAE, inhibiting antigen-specific reactivity and inducing Treg. In addition, the long-term treatment was well tolerated and leading to a prolonged maintenance of tolerogenicity mediated by induction of Breg, reduction of NK cells and activation of immunoregulatory NKT cells. CONCLUSIONS: The outcomes of this study show that the use of antigen-specific f-tolDC promotes multiple and potent tolerogenic mechanisms. Moreover, these cells can be kept frozen maintaining their tolerogenic properties, which is a relevant step for their translation to the clinic. Altogether, vitD3 f-tolDC-MOG is a potential strategy to arrest the autoimmune destruction in MS patients

Cryopreserved vitamin D-3-tolerogenic dendritic cells pulsed with autoantigens as a potential therapy for multiple sclerosis patients

BACKGROUND: Tolerogenic dendritic cells (tolDC) have been postulated as a potent immunoregulatory therapy for autoimmune diseases such as multiple sclerosis (MS). In a previous study, we demonstrated that the administration of antigen-specific vitamin D(3) (vitD3) tolDC in mice showing clinical signs of experimental autoimmune encephalomyelitis (EAE; the animal model of MS) resulted in abrogation of disease progression. With the purpose to translate this beneficial therapy to the clinics, we have investigated the effectivity of vitD3-frozen antigen-specific tolDC pulsed with myelin oligodendrocyte glycoprotein 40-55 peptide (f-tolDC-MOG) since it would reduce the cost, functional variability and number of leukapheresis to perform to the patients. METHODS: Mice showing EAE clinical signs were treated with repetitive doses of f-tolDC-MOG. Tolerogenic mechanisms induced by the therapy were analysed by flow cytometry and T cell proliferation assays. RESULTS: Treatment with f-tolDC-MOG was effective in ameliorating clinical signs of mice with EAE, inhibiting antigen-specific reactivity and inducing Treg. In addition, the long-term treatment was well tolerated and leading to a prolonged maintenance of tolerogenicity mediated by induction of Breg, reduction of NK cells and activation of immunoregulatory NKT cells. CONCLUSIONS: The outcomes of this study show that the use of antigen-specific f-tolDC promotes multiple and potent tolerogenic mechanisms. Moreover, these cells can be kept frozen maintaining their tolerogenic properties, which is a relevant step for their translation to the clinic. Altogether, vitD3 f-tolDC-MOG is a potential strategy to arrest the autoimmune destruction in MS patients

Inmunodeficiencias primarias: inmunopatogenia, infecciones asociadas y estrategias terapéuticas

Las inmunodeficiencias primarias (IDP) son un grupo de defectos genéticos que generan alteración en los mecanismos de defensa tanto innatos como adaptativos, asociados con: 1) ausencia de uno o varios de los componentes celulares, 2) incapacidad para la comunicación de los elementos de la respuesta inmune, así como también en el reconocimiento de antígenos extraños, propios o modificados e 3) incapacidad para la activación de los mecanismos efectores, bien sea por dificultad para alcanzar los tejidos afectados; para promover la polarización de la respuesta inmune tanto proinflamatoria como reguladora; o para liberar mediadores encargados de la destrucción de los agentes invasores. Este complejo grupo de enfermedades condicionan no solo a una susceptibilidad elevada para sufrir infecciones por diferentes agentes infecciosos, sino también a la alteración de los mecanismos homeostáticos y de vigilancia que evitan el desarrollo de enfermedades autoinflamatorias y neoplásicas. En esta revisión se describen parte de estos defectos, sus consecuencias y el abordaje inicial para el estudio y manejo de las infecciones recurrentes. Primary immunodeficiencies: immunopathogenesis, associated infections and therapeutic strategies Abstract Primary immunodeficiencies disorders (PID) are a group of genetic defects that affect both innate and adaptive immune response. PID are associated with: 1) absence of cellular components, 2) impaired connection among components of the immune response, as well as in the recognition of foreign, self or modified antigens, and 3) inappropriate modulation of effectors mechanisms either by inability to reach affected tissues, to promote proinflammatory and regulatory polarization, or perform the clearance of invading agents. PID not only increases the susceptibility to infections by different microorganisms, but also alters the homeostatic mechanisms and immune surveillance, that prevent autoinflammatory and neoplastic diseases. This review describes some of these defects, its consequences and the initial approach to the study and management of recurrent infections

Cryopreserved vitamin D3-tolerogenic dendritic cells pulsed with autoantigens as a potential therapy for multiple sclerosis patients

Altres ajuts: Cost Action BM1305BACKGROUND: Tolerogenic dendritic cells (tolDC) have been postulated as a potent immunoregulatory therapy for autoimmune diseases such as multiple sclerosis (MS). In a previous study, we demonstrated that the administration of antigen-specific vitamin D3 (vitD3) tolDC in mice showing clinical signs of experimental autoimmune encephalomyelitis (EAE; the animal model of MS) resulted in abrogation of disease progression. With the purpose to translate this beneficial therapy to the clinics, we have investigated the effectivity of vitD3-frozen antigen-specific tolDC pulsed with myelin oligodendrocyte glycoprotein 40-55 peptide (f-tolDC-MOG) since it would reduce the cost, functional variability and number of leukapheresis to perform to the patients. METHODS: Mice showing EAE clinical signs were treated with repetitive doses of f-tolDC-MOG. Tolerogenic mechanisms induced by the therapy were analysed by flow cytometry and T cell proliferation assays. RESULTS: Treatment with f-tolDC-MOG was effective in ameliorating clinical signs of mice with EAE, inhibiting antigen-specific reactivity and inducing Treg. In addition, the long-term treatment was well tolerated and leading to a prolonged maintenance of tolerogenicity mediated by induction of Breg, reduction of NK cells and activation of immunoregulatory NKT cells. CONCLUSIONS: The outcomes of this study show that the use of antigen-specific f-tolDC promotes multiple and potent tolerogenic mechanisms. Moreover, these cells can be kept frozen maintaining their tolerogenic properties, which is a relevant step for their translation to the clinic. Altogether, vitD3 f-tolDC-MOG is a potential strategy to arrest the autoimmune destruction in MS patients