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: Next, we asked whether peptide-loaded MHCII molecules (pMHCII) could also be transferred from DCs to LNSCs, and if so, whether these transferred complexes could be functionally presented to CD4+ T cells. To this end, we first loaded DCs with FITC-labeled OVA323-339 peptide and, after thorough washing, co-cultured them with LEC/FRCs. We found efficient transfer of FITC fluorescence to both LECs and FRCs (Fig. 6 A), suggesting that DCs can transfer pMHCII complexes to LNSCs in vitro. Importantly, similar results were obtained using CIITA−/− LEC/FRC cells, ruling out the possibility that endogenous MHCII molecules expressed by LECs and FRCs were loaded with free FITC+ OVA peptide (Fig. 6 B). Consistent with a possible role for exosomes in the transfer of pMHCII to LNSCs, exosomes derived from FITC-labeled OVA323-339-loaded DCs were FITC+ (Fig. 6 C). Importantly, all FITC+ exosomes were MHCII positive, reinforcing the idea that exosomes might transfer pMHCII complexes rather than free peptide (Fig. 6 C).
Affiliation: Department of Pathology and Immunology, University of Geneva Medical School, 1211 Geneva, Switzerland.