CD1d on Myeloid Dendritic Cells Stimulates Cytokine Secretion from and Cytolytic Activity of Vα24JαQ T Cells: A Feedback Mechanism for Immune Regulation (original) (raw)
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CD1d structure and regulation on human thymocytes, peripheral blood T cells,B cells and monocytes
Immunology, 2000
speci®cally recognize CD1d and appear to have immunoregulatory functions. However, the physiological target cells for this T-cell population, and whether alterations in CD1d expression contribute to the regulation of Va24 invt T-cell responses, remain to be determined. A series of antibodies were generated to assess CD1d expression, structure and regulation on human lymphoid and myeloid cells. CD1d was expressed at high levels by human cortical thymocytes and immunoprecipitation analyses showed it to be a 48 000-MW glycosylated protein. However, after solubilization, the majority of the thymocyte CD1d protein, but not CD1d expressed by transfected cells, lost reactivity with monoclonal antibodies (mAbs) against native CD1d, indicating that it was alternatively processed. Moreover, thymocytes were not recognized by CD1d-reactive Va24 invt Tcell clones. Medullary thymocytes and resting peripheral blood T cells were CD1d ± , but low-level CD1d expression was induced on activated T cells. CD1d was expressed by B cells in peripheral blood and lymph node mantle zones, but germinal centres were CD1d ± . Resting monocytes were CD1d + but, in contrast to CD1a, b and c, their surface expression of CD1d was not up-regulated by granulocyte±macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) activation. These results demonstrate constitutive CD1d expression by human professional antigen-presenting cells and that post-translational processing of CD1d may contribute to regulation of the activity of CD1d-speci®c T cells.
CD1d-restricted T-cell subsets and dendritic cell function in autoimmunity
Immunology and Cell Biology, 2004
CD1-restricted T cells have been shown to play a critical role in host defence, tumour surveillance, and maintenance of tolerance. However, immunologic outcomes resulting from activation of CD1d-restricted T cells can be either beneficial or deleterious. A major mechanism by which CD1d-restricted T cells are thought to exert immunoregulatory control is via effects on dendritic cell (DC) differentiation and migration. Important functional subsets of CD1d-restricted T cells are also known to exist and the potential implications for preferential subset activations are discussed.
International Immunology, 2004
We previously demonstrated that tumor necrosis factor (TNF)-a-matured CD16 ÿ and CD16 1 human monocyte-derived dendritic cells (16ÿmDC and 161mDC) differentially stimulate naive CD4 1 lymphocytes by inducing Th1-and Th2-like responses, respectively. Here, we further characterized the role of different DC maturation factors on Th polarization. Immature 161mDC and 16ÿmDC (iDC) obtained by culture of purified monocytes with GM-CSF and IL-4 were maturated with (i) Toll-like receptor (TLR) ligands [lipopolysaccharide (LPS)], (ii) lymphocyte-derived (soluble CD40 ligand, IFN-c) and (iii) endogenous inflammatory stimuli [TNF-a, prostaglandin (PG)E 2 ]. After activation with these stimuli, DC secrete IL-12 only in presence of LPS, and 161mDC produced lower amounts of IL-12 and IL-10 than 16ÿmDC. Allogeneic CD4 1 CD45RO ÿ lymphocytes co-cultured with 161mDC secreted higher levels of IL-4 and IL-10 than those co-cultured with 16ÿmDC, regardless of the maturation stimuli. Results were similar when DC were activated with TLR-2 or TLR-3 ligands. The higher induction of IL-4 by 161mDC was primarily dependent on IL-12, IL-4 and IL-10. IFN-c production by CD4 1 T cells was similar with all the conditions except with LPS-161mDC, which induced reduced amounts of this cytokine. Those differences were totally eliminated by neutralization of IL-12, IL-4 or IL-10. Finally, 16ÿmDC could reverse the Th2 phenotype of already committed lymphocytes toward a Th1 pattern in short-term cultures, whereas 161mDC had less ability to skew this phenotype. These results indicate that 161mDC elicit superior Th2 responses independently of the maturation factors that they received, and suggest that they could represent an important population of regulatory DC.
CD 1 d restriction and Th 1 / Th 2 / Th 17 cytokine secretion by human V δ 3 T cells
2013
Human γδ T cells expressing the Vδ3 TCR comprise a minor lymphocyte subset in blood but are enriched in liver and in patients with some chronic viral infections and leukemias. We analysed the frequencies, phenotypes, restriction elements and functions of fresh and expanded peripheral blood Vδ3 T cells. Vδ3 T cells accounted for ~0.2% of circulating T cells, included CD4+, CD8+ and CD4−CD8− subsets, and variably expressed CD56, CD161, HLA-DR and NKG2D, but not NKG2A nor NKG2C. Vδ3 T cells were sorted and expanded by mitogen stimulation in the presence of IL-2. Expanded Vδ3 T cells recognised CD1d, but not CD1a, CD1b nor CD1c. Upon activation, they killed CD1d+ target cells, released Th1, Th2 and Th17 cytokines and induced maturation of dendritic cells into APCs. Thus, Vδ3 T cells are glycolipid-reactive T cells with distinct antigen specificities but functional similarities to natural killer T cells.
Regulation of T cell cytokine production by dendritic cells
Immunology and Cell Biology, 2000
Previous work has established that the dendritic cells (DC) of mouse spleen regulate the IL-2 production, and hence the extent of proliferation, of the CD8 T cells they activate. It is now reported here that interaction of primary CD8 T cells with splenic CD8α -DC induced much higher production of IL-3, IFN-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF), as well as IL-2, than did interaction with CD8α + splenic DC. Furthermore, the CD8α -DC also induced higher levels of IL-2, IL-3 and IL-10 production in primary CD4 T cells, compared with that induced by CD8α + DC. These quantitative differences did not involve qualitative shifts in the type of cytokine produced. Interleukin-4 production remained low in all the primary T cell cultures and restimulation experiments in secondary cultures did not reveal any bias in the cytokine production profile. When exogenous IL-2 was added to the primary cultures to ensure equal proliferation in response to CD8αor CD8α + DC, the higher level of production of IL-3, IFN-γ and GM-CSF induced by CD8α -DC was maintained. Thus, this general control of T cell cytokine production by splenic DC involves factors additional to those that govern activation of T cells into cell cycle.
CD1-mediated γ/δ T Cell Maturation of Dendritic Cells
Journal of Experimental Medicine, 2002
Immature myeloid dendritic cells (DCs) express only low levels of major histocompatibility complex (MHC) class II but express high levels of CD1 a, b, and c antigen-presenting molecules at the cell surface. As Vδ1+ γ/δ T cells are the main tissue subset of γ/δ T cells and they are known to recognize CD1c in the absence of specific foreign antigen recognition, we examined the possible interaction of these T cells with immature DCs. We show that CD1-restricted γ/δ T cells can mediate the maturation of DCs. DC maturation required cell–cell contact and could be blocked by antibodies against CD1c. The maturation process was partially mediated by tumor necrosis factor α. Importantly, immature DCs matured in the presence of lipopolysaccharide and CD1-restricted γ/δ T cells produced bioactive interleukin-12p70. In addition, these DCs were able to efficiently present peptide antigens to naive CD4+ T cells. CD1-restricted γ/δ T cell recognition of immature DCs provides the human immune system...
The Journal of Immunology, 2005
Suppressor of cytokine signaling (SOCS1/JAB) has been shown to play an important role in regulating dendritic cell (DC) function and suppressing inflammatory diseases and systemic autoimmunity. However, role of SOCS1 in DCs for the initiation of Th cell response has not been clarified. Here we demonstrate that SOCS1-deficient DCs induce stronger Th1-type responses both in vitro and in vivo. SOCS1-deficient DCs induced higher IFN-γ production from naive T cells than wild-type (WT) DCs in vitro. Lymph node T cells also produced a higher amount of IFN-γ when SOCS1-deficient bone marrow-derived DCs (BMDCs) were transferred in vivo. Moreover, SOCS1−/− BMDCs raised more effective anti-tumor immunity than WT BMDCs. Microarray analysis revealed that IFN-inducible genes were highly expressed in SOCS1-deficient DCs without IFN stimulation, suggesting hyper STAT1 activation in SOCS1−/− DCs. These phenotypes of SOCS1-deficient DCs were similar to those of CD8α+ DCs, and in the WT spleen, SOCS1 ...
Journal of Leukocyte Biology, 2006
Interleukin (IL)-2 plays an important role in the control of the immune responses, and it is released in a variety of tissues in response to inflammatory stimuli. As monocytes and mature dendritic cells (DCs) express CD25, the high-affinity subunit of IL-2 receptor, we examined the effect of exogenous IL-2 on the in vitro generation and maturation of DCs from monocytes. Human monocyte-derived DCs (MDDCs) were generated by culturing monocytes with granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-4 (DCs) in the presence or absence of IL-2. The cytokine was added at the beginning and after 5 days of culture. Our findings indicate that IL-2 does induce monocytes to differentiate into DCs with the same morphology and phenotype of that obtained in the presence of GM-CSF and IL-4 alone but with some distinctive functional properties. DCs differentiated in the presence of IL-2 secreted significantly more IL-1, tumor necrosis factor ␣, and IL-12 p70 in response to lipopolysaccharide stimulation and induced allogeneic, naïve T cells to release a significantly higher amount of interferon-␥ if compared with DCs obtained by culturing monocytes with GM-CSF and IL-4. These results indicate unrecognized effects of IL-2 on human MDDCs and suggest that an IL-2-rich environment during differentiation and maturation of DCs can modify their T helper cell-inducing properties.