Dysregulated CD1 profile in myeloid dendritic cells in CVID is normalized by IVIg treatment.

The CD1 proteins are major histocompatibility complex class I-like molecules specialized in presenting lipid and glycolipid antigens to T cells. Group I CD1s include CD1a, CD1b, and CD1c and present bacterial antigens to a diverse repertoire of pathogen-specific T cells. In contrast, CD1d presents endogenous and exogenous ligands to invariant natural killer T cells. Different subsets of dendritic cells (DCs) express distinct CD1 profiles. Myeloid DCs (mDCs) in the blood express CD1d, whereas Langerhans cells in the skin express CD1a, suggesting that signals present in the microenvironment regulate these antigen presentation pathways. We have reported previously that IgG regulates the expression of CD1 molecules on human DCs in vitro, via an CD32a (FcgRIIa)–dependent mechanism. In the present study, we took advantage of the low IgG levels in treatment-naı̈ve patients with common variable immunodeficiency (CVID) to investigate if IgG might regulate the CD1 expression profile also in vivo. Peripheral blood mononuclear cells isolated from 13 patients newly diagnosed with CVID according to the criteria established by the Pan-American Group for Immunodeficiency before the onset of intravenous immunoglobulin (IVIg) replacement therapy were analyzed by flow cytometry. Approval was obtained from the University of Sao Paulo institutional review board for these studies, and informed consent was provided according to the Declaration of Helsinki. mDCs were defined as CD3-CD14-CD19-CD56-CD11c1 HLA-DR1 (Figure 1A). The proportion of mDCs expressing CD1c was elevated in treatment-naı̈ve patients with CVID compared with healthy control participants (Figure 1B). Interestingly, this subset bias was normalized after 12 months of IVIg treatment (Figure 1B). Next, we investigated the expression of CD1a, CD1b, and CD1d on the CD1c1 mDC subset. As expected, CD1a and CD1b were essentially undetectable on CD1c1 mDCs from healthy control participants (Figure 1C-D), whereas CD1d was ubiquitously