Immunosuppression induced by immature dendritic cells is mediated by TGF-beta/IL-10 double-positive CD4+ regulatory T cells. Export

@article{citeulike:4116446, abstract = {Dendritic cells (DC) have important functions in T cell immunity and T cell tolerance. Previously, it was believed that T cell unresponsiveness induced by immature DC (iDC) is caused by the absence of inflammatory signals in steady-state in vivo conditions and by the low expression levels of costimulatory molecules on iDC. However, a growing body of evidence now indicates that iDC can also actively maintain peripheral T cell tolerance by the induction and/or stimulation of regulatory T cell populations. In this study, we investigated the in vitro T cell stimulatory capacity of iDC and mature DC (mDC) and found that both DC types induced a significant increase in the number of transforming growth factor (TGF)-beta and interleukin (IL)-10 double-positive CD4(+) T cells within 1 week of autologous DC/T cell co-cultures. In iDC/T cell cultures, where antigen-specific T cell priming was significantly reduced as compared to mDC/T cell cultures, we demonstrated that the tolerogenic effect of iDC was mediated by soluble TGF-beta and IL-10 secreted by CD4(+)CD25(-)FOXP3(-) T cells. In addition, the suppressive capacity of CD4(+) T cells conditioned by iDC was transferable to already primed antigen-specific CD8(+) T cell cultures. In contrast, addition of CD4(+) T cells conditioned by mDC to primed antigen-specific CD8(+) T cells resulted in enhanced CD8(+) T cell responses, notwithstanding the presence of TGF-beta(+)/IL-10(+) T cells in the transferred fraction. In summary, we hypothesize that DC have an active role in inducing immunosuppressive cytokine-secreting regulatory T cells. We show that iDC-conditioned CD4(+) T cells are globally immunosuppressive, while mDC induce globally immunostimulatory CD4(+) T cells. Furthermore, TGF-beta(+)/IL-10(+) T cells are expanded by DC independent of their maturation status, but their suppressive function is dependent on immaturity of DC.}, author = {Cools, N. and Van Tendeloo, V. F. and Smits, E. L. and Lenjou, M. and Nijs, G. and Van Bockstaele, D. R. and Berneman, Z. N. and Ponsaerts, P.}, citeulike-article-id = {4116446}, citeulike-linkout-0 = {http://dx.doi.org/10.1111/j.1582-4934.2007.00084.x}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18419605}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18419605}, doi = {10.1111/j.1582-4934.2007.00084.x}, issn = {1582-1838}, journal = {Journal of cellular and molecular medicine}, keywords = {confounder, dendritic, dod, treg-action, treg-cancer, tumour}, month = {April}, number = {2}, pages = {690--700}, posted-at = {2009-03-01 17:34:56}, priority = {2}, title = {Immunosuppression induced by immature dendritic cells is mediated by TGF-beta/IL-10 double-positive CD4+ regulatory T cells.}, url = {http://dx.doi.org/10.1111/j.1582-4934.2007.00084.x}, volume = {12}, year = {2008} }

TY - JOUR ID - citeulike:4116446 L3 - citeulike-article-id:4116446 N2 - Dendritic cells (DC) have important functions in T cell immunity and T cell tolerance. Previously, it was believed that T cell unresponsiveness induced by immature DC (iDC) is caused by the absence of inflammatory signals in steady-state in vivo conditions and by the low expression levels of costimulatory molecules on iDC. However, a growing body of evidence now indicates that iDC can also actively maintain peripheral T cell tolerance by the induction and/or stimulation of regulatory T cell populations. In this study, we investigated the in vitro T cell stimulatory capacity of iDC and mature DC (mDC) and found that both DC types induced a significant increase in the number of transforming growth factor (TGF)-beta and interleukin (IL)-10 double-positive CD4(+) T cells within 1 week of autologous DC/T cell co-cultures. In iDC/T cell cultures, where antigen-specific T cell priming was significantly reduced as compared to mDC/T cell cultures, we demonstrated that the tolerogenic effect of iDC was mediated by soluble TGF-beta and IL-10 secreted by CD4(+)CD25(-)FOXP3(-) T cells. In addition, the suppressive capacity of CD4(+) T cells conditioned by iDC was transferable to already primed antigen-specific CD8(+) T cell cultures. In contrast, addition of CD4(+) T cells conditioned by mDC to primed antigen-specific CD8(+) T cells resulted in enhanced CD8(+) T cell responses, notwithstanding the presence of TGF-beta(+)/IL-10(+) T cells in the transferred fraction. In summary, we hypothesize that DC have an active role in inducing immunosuppressive cytokine-secreting regulatory T cells. We show that iDC-conditioned CD4(+) T cells are globally immunosuppressive, while mDC induce globally immunostimulatory CD4(+) T cells. Furthermore, TGF-beta(+)/IL-10(+) T cells are expanded by DC independent of their maturation status, but their suppressive function is dependent on immaturity of DC. IS - 2 JF - Journal of cellular and molecular medicine SN - 1582-1838 EP - 700 TI - Immunosuppression induced by immature dendritic cells is mediated by TGF-beta/IL-10 double-positive CD4+ regulatory T cells. VL - 12 SP - 690 KW - confounder KW - dendritic KW - dod KW - treg-action KW - treg-cancer KW - tumour AU - Cools, N AU - Van Tendeloo, VF AU - Smits, EL AU - Lenjou, M AU - Nijs, G AU - Van Bockstaele, DR AU - Berneman, ZN AU - Ponsaerts, P PY - 2008/04// UR - http://dx.doi.org/10.1111/j.1582-4934.2007.00084.x ER -