TGFbeta inhibits CD1d expression on dendritic cells.

Abstract

The CD1 family of cell surface glycoprotein has been demonstrated to be a third lineage of antigen-presenting molecules for specific T cell responses. They present lipidic, glycolipidic antigen and hydrophobic peptide to T cells. CD1d restricted T cells play a role in autoimmune disease and in tumor immunity. Transforming growth factor beta (TGFbeta), a member of the family of polypeptide growth factors synthetized by human keratinocytes, has inhibitory effects on proliferation and differentiation of immune cells, especially on CD1d-restricted natural killer T cells. These properties led us to investigate the role of TGFbeta in CD1d expression on dendritic cells (DC), which are known to play a key role in initiation of the immune response. Here, we observed CD1d molecules on DC developed from PBMC with GM-CSF and IL4 but not with GM-CSF, IL4 and TGFbeta for 7 d. RT-PCR and FACS analysis (mAb 42.1) performed at various stages of differentiation on CD34+ HPC show that CD1d mRNA levels and CD1d molecule expression at the cell surface decreased progressively during the differentiation process. Thus, while committing DC-precursors differentiation toward the Langerhans cell (LC) pathway, TGFbeta likely inhibits CD1d transcription. Therefore, LC freshly recovered from epidermal sheet were evaluated by flow cytometry. In accordance with in vitro observation, they did not expressed measurable levels of CD1d molecules at the cell membrane. Thus, TGFbeta produced by keratinocytes contribute to selectively downregulate CD1d expression on intraepidermal-resident LC.