Anti-CD1c Monoclonal antibody, clone M272 [APC]

Dendritic cells (DCs) are highly potent antigen-presenting cells (APCs) and play a vital role in stimulating naive T cells. Treatment of human blood monocytes with the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 stimulates them to develop into immature dendritic cells (iDCs) in vitro. DCs generated by this pathway have a high capacity to prime and activate resting T cells and prominently express CD1 antigen-presenting molecules on the cell surface. The presence of human serum during the differentiation of iDCs from monocytes inhibits the expression of CD1a, CD1b and CD1c, but not CD1d. Correspondingly, T cells that are restricted by CD1c showed poor responses to DCs that were generated in the presence of human serum, while the responses of CD1d-restricted T cells were enhanced. We chemically fractionated human serum to isolate the bioactive factors that modulate surface expression of CD1 proteins during monocyte to DC differentiation. The human serum components that affected CD1 expression partitioned with polar organic soluble fractions. Lysophosphatidic acid and cardiolipin were identified as lipids present in normal human serum that potently modulate CD1 expression. Control of CD1 expression was mediated at the level of gene transcription and correlated with activation of the peroxisome proliferator-activated receptor (PPAR) nuclear hormone receptors. These findings indicate that the ability of human DCs to present lipid antigens to T cells through expression of CD1 molecules is sensitively regulated by lysophosphatidic acid and cardiolipin in serum, which are ligands that can activate PPAR transcription factors.

PURPOSE. Myeloid dendritic cells (mDCs) play an important role in autoimmune diseases. However, the role of blood CD1c(+) myeloid dendritic cells 1 (mDC1s), the subset of human blood mDCs, is not well understood in noninfectious uveitis. METHODS. Fresh peripheral blood samples from human noninfectious uveitis patients (n = 32) and healthy controls (HCs) (n = 64) were stained with FITC-Lineage 1 (Lin1), PERCP-HLADR, and PE-CD1c antibodies. The levels of mDC1 were quantified by using flow cytometric analysis. Longitudinal data from patients (n = 16) were analyzed to correlate the levels of mDC1 with disease activity. RESULTS. Blood CD1c(+) mDC1 and its subpopulation, CD1c(hi) mDC1, were increased in uveitis patients compared with HCs. Longitudinal data demonstrated that both the CD1c(+) mDC1 and CD1c(hi) mDC1 subpopulation reflected a dynamic change in clinical uveitis activity: CD1c expression was increased in active uveitis but decreased when uveitis became inactive. CONCLUSIONS. Given these observations, an alteration in blood CD1c(+) mDC1 and the CD1c(hi) mDC1 subpopulation could be a potential biomarker to monitor clinical uveitis activity within patients.