The brain as an immune privileged site: dendritic cells of the central nervous system inhibit T cell activation

Abstract

Dendritic cells (DC) are unique in their ability to prime naive T cells and initiate adaptive immunity. In recent years, DC were identified in the inflamed central nervous system (CNS), but their role in the initiation or regulation of the tissue specific immune response is unknown. As shown here, DC isolated from mice with experimental autoimmune encephalomyelitis (EAE) exhibit a maturational phenotype similar to immature bone marrow-derived DC or splenic DC as characterized by intermediate surface MHC class II and low expression of the costimulatory molecule CD80. However, they are unable to prime naive T cells. Moreover, they inhibit T cell proliferation stimulated by mature bone marrow-derived DC. TGF g , IL-10 and TRAIL were found to significantly contribute to the CNS-DC-mediated inhibition of allo-T cell proliferation. Thus CNS-DC may be the key responsibles for maintaining immune privilege within the inflamed CNS.

Site‐specific anti‐tumor immunity: Differences in DC function, TGF‐β production and numbers of intratumoral Foxp3+ Treg

“…The function of CNS-derived DC has been analyzed in murine models of autoimmune and infectious diseases, with a variety of functions observed for these DC, ranging from inhibition of T-cell activation [32] to promotion of disease spreading [33]. Likewise, TIDC in non-glioma tumors have been described as playing several roles in the anti-tumor response.…”

“…Proliferation and inhibition assays were performed as described previously [32]. Briefly, CD4 1 T cells were isolated from BALB/c or OT-II spleens using anti-mouse CD4-biotin (BD Bioscience) and CELLection biotin binder beads (Dynal/Invitrogen, Basel, Switzerland).…”

“…For proliferation assays, 10 5 T cells per well were cultured in a 96-well U-bottom plate (Falcon, BD) in the presence of titrated numbers of various DC preparations in 200 mL X-VIVO 20 medium (BioWhittaker, Walkersville, MD), supplemented with 2 mM acetyl-alanyl-glutamine, 1 Â MEM nonessential amino acids (Invitrogen), 1 mM sodium pyruvate (MP Biomedicals, Solon, OH), 50 mM b-mercaptoethanol (Sigma) and 25 mg/ mL gentamycin. Mature BMDC were generated by cultivation of BM cells in GM-CSF and induction of maturation by LPS as previously described [32]. For the inhibition assays, 10 5 CD4 1 T cells and 10 4 mature BMDC were cultured in the presence of titrating numbers of various DC preparations.…”

TRAIL and immunity: more than a license to kill tumor cells

“…Human bcells express TRAIL receptors and sensitivity to TRAILinduced apoptosis can be amplified by inhibition of protein synthesis or removal of TRAIL-R3. 33 Finally, TRAIL has also been shown to mediate a regulatory function during the pathogenesis of experimental allergic encephalomyelitis (EAE), 34 an animal model for multiple sclerosis in humans. Apart from this impressive regulatory potential of TRAIL in the regulation of autoreactive lymphocytes, it cannot be excluded that TRAIL, similar to FasL, also participates in the direct tissue destruction observed in most autoimmune dieases.…”

Pulmonary stromal cells induce the generation of regulatory DC attenuating T‐cell‐mediated lung inflammation

“…Up to now, regulatory DCreg were generated by culturing imDC in the presence of immunosuppressive cytokines such as IL-10 and TGF-b or immunomodulatory drugs [4][5][6], which does not represent the in vivo physiologic conditions of DCreg in the organ microenvironment. More and more data show that the microenvironment in certain tissues has the ability to induce DC development [7][8][9][10] and also affects the function of DC; for example, DC in brain and kidney display regulatory functions but not T-cell-activating functions [11,12]. Our previous studies demonstrate that endothelial splenic stromal cells, which are used to mimic the in vivo splenic microenvironment, can promote the proliferation of mature DC (maDC) [7] and hematopoietic stem cells [8], driving them to à These authors contributed equally to this work.…”