Lymph node stromal cells acquire peptide-MHCII complexes from dendritic cells and induce antigen-specific CD4⁺ T cell tolerance.
Bottom Line: Although LNSCs express MHCII, it is unknown whether they can also impact CD4(+) T cell functions.We show that the promoter IV (pIV) of class II transactivator (CIITA), the master regulator of MHCII expression, controls endogenous MHCII expression by LNSCs.Our data reveals a novel, alternative mechanism where LN-resident stromal cells tolerize CD4(+) T cells through the presentation of self-antigens via transferred peptide-MHCII complexes of DC origin.
Affiliation: Department of Pathology and Immunology, University of Geneva Medical School, 1211 Geneva, Switzerland.Show MeSH
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Mentions: To investigate whether MHCII transfer from DCs to LNSCs relies on active processes, isolated LN LEC/FRC cultures were co-cultured with paraformaldehyde (PFA)-pretreated DCs. These paralyzed DCs entirely lost their ability to transfer MHCII to LECs and FRCs (Fig. 5 A), suggesting an active transfer of MHCII from donor to recipient cells. To investigate whether this process was cell–cell contact dependent, we co-cultured DCs and LEC/FRCs in different compartments separated by a culture insert membrane, and observed a dramatic reduction of MHCII expression on LECs and FRCs (Fig. 5 B). However, small amounts of MHCII were detectable on these cells (Fig. 5 B), suggesting that DC-derived vesicles might also be involved in transferring MHCII molecules in vitro. Indeed, DC-derived exosomes have been previously described to mediate intercellular transfer of surface proteins (Davis, 2007). To determine whether exosomes were involved in the process of MHCII transfer from DCs to LNSCs, we isolated and purified exosomes from cultured DCs as previously described (Théry et al., 2002). We found that DC-derived exosomes were positive for MHCII expression (Fig. 5 C). When DC-derived exosomes were added to LEC/FRC cultures, MHCII expression increased in a dose-dependent manner on both LECs and FRCs (Fig. 5 D), but to a lesser extent compared with DCs (Fig. 5 D).
Affiliation: Department of Pathology and Immunology, University of Geneva Medical School, 1211 Geneva, Switzerland.