TY - JOUR
T1 - Regulation of Rat and Human T-Cell Immune Response by Pharmacologically Modified Dendritic Cells
AU - Fazekasova, Henrieta
AU - Golshayan, Dela
AU - Read, Joseph
AU - Tsallios, Aristotle
AU - Tsang, Julia Yuen-Shan
AU - Dorling, Anthony
AU - George, Andrew J. T.
AU - Lechler, Robert I.
AU - Lombardi, Giovanna
AU - Mirenda, Vincenzo
PY - 2009/6/15
Y1 - 2009/6/15
N2 - Background. The central function of dendritic cells (DC) in inducing and preventing immune responses makes them ideal therapeutic targets for the induction of immunologic tolerance. In a rat in vivo model, we showed that dexamethasone-treated DC (Dex-DC) induced indirect pathway-mediated regulation and that CD4(+)CD25(+) T cells were involved in the observed effects. The aim of the present study was to investigate the mechanisms underlying the acquired immunoregulatory properties of Dex-DC in the rat and human experimental systems.
Methods. After treatment with dexamethasone (Dex), the immunogenicity of Dex-DC was analyzed in T-cell proliferation and two-step hyporesponsiveness induction assays. After carboxyfluorescein diacetate succinimidyl ester labeling, CD4(+)CD25(+) regulatory T-cell expansion was analyzed by flow cytometry, and cytokine secretion was measured by ELISA.
Results. In this Study, we demonstrate in vitro that rat Dex-DC induced selective expansion of CD4(+)CD25(+) regulatory T cells, which were responsible for alloantigen-specific hyporesponsiveness. The induction of regulatory T-cell division by rat Dex-DC was due to secretion of interleukin (IL-2) by DC. Similarly, in human studies, monocyte-derived Dex-DC were also poorly immunogenic, were able to induce T-cell anergy in vitro, and expand a population of T cells with regulatory functions. This was accompanied by a change in the cytokine profile in DC and T cells in favor of IL-10.
Conclusion. These data suggest that Dex-DC induced tolerance by different mechanisms in the two systems studied. Both rat and human Dex-DC were able to induce and expand regulatory T cells, which occurred in an IL-2 dependent manner in the rat system.
AB - Background. The central function of dendritic cells (DC) in inducing and preventing immune responses makes them ideal therapeutic targets for the induction of immunologic tolerance. In a rat in vivo model, we showed that dexamethasone-treated DC (Dex-DC) induced indirect pathway-mediated regulation and that CD4(+)CD25(+) T cells were involved in the observed effects. The aim of the present study was to investigate the mechanisms underlying the acquired immunoregulatory properties of Dex-DC in the rat and human experimental systems.
Methods. After treatment with dexamethasone (Dex), the immunogenicity of Dex-DC was analyzed in T-cell proliferation and two-step hyporesponsiveness induction assays. After carboxyfluorescein diacetate succinimidyl ester labeling, CD4(+)CD25(+) regulatory T-cell expansion was analyzed by flow cytometry, and cytokine secretion was measured by ELISA.
Results. In this Study, we demonstrate in vitro that rat Dex-DC induced selective expansion of CD4(+)CD25(+) regulatory T cells, which were responsible for alloantigen-specific hyporesponsiveness. The induction of regulatory T-cell division by rat Dex-DC was due to secretion of interleukin (IL-2) by DC. Similarly, in human studies, monocyte-derived Dex-DC were also poorly immunogenic, were able to induce T-cell anergy in vitro, and expand a population of T cells with regulatory functions. This was accompanied by a change in the cytokine profile in DC and T cells in favor of IL-10.
Conclusion. These data suggest that Dex-DC induced tolerance by different mechanisms in the two systems studied. Both rat and human Dex-DC were able to induce and expand regulatory T cells, which occurred in an IL-2 dependent manner in the rat system.
U2 - 10.1097/TP.0b013e3181a5504c
DO - 10.1097/TP.0b013e3181a5504c
M3 - Article
VL - 87
SP - 1617
EP - 1628
JO - Transplantation
JF - Transplantation
IS - 11
ER -