Cyclosporine preconditions dendritic cells during differentiation and reduces IL-2 and IL-12 production following activation: A potential tolerogenic effect

D. Sauma, A. Fierro, J. R. Mora, A. M. Lennon-Duménil, M. R. Bono, M. Rosemblatt, J. Morales

Resultado de la investigación: Article

32 Citas (Scopus)

Resumen

The mode of action of cyclosporine (CsA) has been ascribed to its capacity to inhibit IL-2 and IFNγ production by T cells, two cytokines implicated in allograft rejection. Recently, it has been reported that upon activation, dendritic cells (DCs) exhibit transient production of IL-2, a property that appears to be related to their capacity to initiate immune responses. On the other hand, DCs can generate signals determining Th1/Th2 polarizing effects, an effect that can drastically influence the outcome of organ transplant. The purpose of the present study was to investigate the effect of CsA on cytokine production by immature and mature DCs. DC precursors from mouse bone marrow were induced to differentiate by incubation with GM-CSF for 5 days followed by activation with LPS for 4 hours. CsA was added at different times during this process. Our results show that when CsA is added during the differentiation period following activation with LPS, IL-2 and IL-12 secretion are significantly reduced without affecting the evolution of the DC. Conversely, CsA had no effect when added during the LPS activation period. These results show that CsA affects DCs before they receive the final activation stimulus, preconditioning them to antigen stimulation. This preconditioning of DCs by calcineurin-inhibiting drugs conceptually integrates the mode of action of CsA with the tolerogenic and T-cell polarization function ascribed to DCs. These results may be especially meaningful for the future design of immunosuppressive protocols.

Idioma originalEnglish
Páginas (desde-hasta)2515-2517
Número de páginas3
PublicaciónTransplantation Proceedings
Volumen35
N.º7
DOI
EstadoPublished - nov 2003

Huella dactilar

Interleukin-12
Dendritic Cells
Cyclosporine
Interleukin-2
Cell Differentiation
Cytokines
T-Lymphocytes
Calcineurin
Granulocyte-Macrophage Colony-Stimulating Factor
Immunosuppressive Agents
Allografts
Bone Marrow
Transplants
Antigens
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Citar esto

Sauma, D. ; Fierro, A. ; Mora, J. R. ; Lennon-Duménil, A. M. ; Bono, M. R. ; Rosemblatt, M. ; Morales, J. / Cyclosporine preconditions dendritic cells during differentiation and reduces IL-2 and IL-12 production following activation : A potential tolerogenic effect. En: Transplantation Proceedings. 2003 ; Vol. 35, N.º 7. pp. 2515-2517.
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abstract = "The mode of action of cyclosporine (CsA) has been ascribed to its capacity to inhibit IL-2 and IFNγ production by T cells, two cytokines implicated in allograft rejection. Recently, it has been reported that upon activation, dendritic cells (DCs) exhibit transient production of IL-2, a property that appears to be related to their capacity to initiate immune responses. On the other hand, DCs can generate signals determining Th1/Th2 polarizing effects, an effect that can drastically influence the outcome of organ transplant. The purpose of the present study was to investigate the effect of CsA on cytokine production by immature and mature DCs. DC precursors from mouse bone marrow were induced to differentiate by incubation with GM-CSF for 5 days followed by activation with LPS for 4 hours. CsA was added at different times during this process. Our results show that when CsA is added during the differentiation period following activation with LPS, IL-2 and IL-12 secretion are significantly reduced without affecting the evolution of the DC. Conversely, CsA had no effect when added during the LPS activation period. These results show that CsA affects DCs before they receive the final activation stimulus, preconditioning them to antigen stimulation. This preconditioning of DCs by calcineurin-inhibiting drugs conceptually integrates the mode of action of CsA with the tolerogenic and T-cell polarization function ascribed to DCs. These results may be especially meaningful for the future design of immunosuppressive protocols.",
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Cyclosporine preconditions dendritic cells during differentiation and reduces IL-2 and IL-12 production following activation : A potential tolerogenic effect. / Sauma, D.; Fierro, A.; Mora, J. R.; Lennon-Duménil, A. M.; Bono, M. R.; Rosemblatt, M.; Morales, J.

En: Transplantation Proceedings, Vol. 35, N.º 7, 11.2003, p. 2515-2517.

Resultado de la investigación: Article

TY - JOUR

T1 - Cyclosporine preconditions dendritic cells during differentiation and reduces IL-2 and IL-12 production following activation

T2 - A potential tolerogenic effect

AU - Sauma, D.

AU - Fierro, A.

AU - Mora, J. R.

AU - Lennon-Duménil, A. M.

AU - Bono, M. R.

AU - Rosemblatt, M.

AU - Morales, J.

PY - 2003/11

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N2 - The mode of action of cyclosporine (CsA) has been ascribed to its capacity to inhibit IL-2 and IFNγ production by T cells, two cytokines implicated in allograft rejection. Recently, it has been reported that upon activation, dendritic cells (DCs) exhibit transient production of IL-2, a property that appears to be related to their capacity to initiate immune responses. On the other hand, DCs can generate signals determining Th1/Th2 polarizing effects, an effect that can drastically influence the outcome of organ transplant. The purpose of the present study was to investigate the effect of CsA on cytokine production by immature and mature DCs. DC precursors from mouse bone marrow were induced to differentiate by incubation with GM-CSF for 5 days followed by activation with LPS for 4 hours. CsA was added at different times during this process. Our results show that when CsA is added during the differentiation period following activation with LPS, IL-2 and IL-12 secretion are significantly reduced without affecting the evolution of the DC. Conversely, CsA had no effect when added during the LPS activation period. These results show that CsA affects DCs before they receive the final activation stimulus, preconditioning them to antigen stimulation. This preconditioning of DCs by calcineurin-inhibiting drugs conceptually integrates the mode of action of CsA with the tolerogenic and T-cell polarization function ascribed to DCs. These results may be especially meaningful for the future design of immunosuppressive protocols.

AB - The mode of action of cyclosporine (CsA) has been ascribed to its capacity to inhibit IL-2 and IFNγ production by T cells, two cytokines implicated in allograft rejection. Recently, it has been reported that upon activation, dendritic cells (DCs) exhibit transient production of IL-2, a property that appears to be related to their capacity to initiate immune responses. On the other hand, DCs can generate signals determining Th1/Th2 polarizing effects, an effect that can drastically influence the outcome of organ transplant. The purpose of the present study was to investigate the effect of CsA on cytokine production by immature and mature DCs. DC precursors from mouse bone marrow were induced to differentiate by incubation with GM-CSF for 5 days followed by activation with LPS for 4 hours. CsA was added at different times during this process. Our results show that when CsA is added during the differentiation period following activation with LPS, IL-2 and IL-12 secretion are significantly reduced without affecting the evolution of the DC. Conversely, CsA had no effect when added during the LPS activation period. These results show that CsA affects DCs before they receive the final activation stimulus, preconditioning them to antigen stimulation. This preconditioning of DCs by calcineurin-inhibiting drugs conceptually integrates the mode of action of CsA with the tolerogenic and T-cell polarization function ascribed to DCs. These results may be especially meaningful for the future design of immunosuppressive protocols.

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