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Plasmacytoid dendritic cells and type 1 interferon promote peripheral expansion of forkhead box protein 3+ regulatory T cells specific for the ubiquitous RNA-binding nuclear antigen La/Sjögren's syndrome (SS)-B
- Source :
- Clinical and Experimental Immunology. 186:18-29
- Publication Year :
- 2016
- Publisher :
- Oxford University Press (OUP), 2016.
-
Abstract
- Summary RNA-binding nuclear antigens are a major class of self-antigen to which immune tolerance is lost in rheumatic diseases. Serological tolerance to one such antigen, La/Sjögren's syndrome (SS)-B (La), is controlled by CD4+ T cells. This study investigated peripheral tolerance to human La (hLa) by tracking the fate of hLa-specific CD4+ T cells expressing the transgenic (Tg) 3B5.8 T cell receptor (TCR) after adoptive transfer into lymphocyte-replete recipient mice expressing hLa as a neo-self-antigen. After initial antigen-specific cell division, hLa-specific donor CD4+ T cells expressed forkhead box protein 3 (FoxP3). Donor cells retrieved from hLa Tg recipients displayed impaired proliferation and secreted interleukin (IL)−10 in vitro in response to antigenic stimulation. Transfer of highly purified FoxP3-negative donor cells demonstrated that accumulation of hLa-specific regulatory T cells (Treg) was due primarily to expansion of small numbers of donor Treg. Depletion of recipient plasmacytoid dendritic cells (pDC), but not B cells, severely hampered the accumulation of FoxP3+ donor Treg in hLa Tg recipients. Recipient pDC expressed tolerogenic markers and higher levels of co-stimulatory and co-inhibitory molecules than B cells. Adoptive transfer of hLa peptide-loaded pDC into mice lacking expression of hLa recapitulated the accumulation of hLa-specific Treg. Blockade of the type 1 interferon (IFN) receptor in hLa Tg recipients of hLa-specific T cells impaired FoxP3+ donor T cell accumulation. Therefore, peripheral expansion of Treg specific for an RNA-binding nuclear antigen is mediated by antigen-presenting pDC in a type 1 IFN-dependent manner. These results reveal a regulatory function of pDC in controlling autoreactivity to RNA-binding nuclear antigens.
- Subjects :
- 0301 basic medicine
Adoptive cell transfer
Regulatory T cell
T cell
Immunology
Epitopes, T-Lymphocyte
Mice, Transgenic
Plasmacytoid dendritic cell
Lymphocyte Activation
Autoantigens
T-Lymphocytes, Regulatory
Immune tolerance
Mice
03 medical and health sciences
0302 clinical medicine
Antigen
medicine
Animals
Immunology and Allergy
B-Lymphocytes
Chemistry
Peripheral tolerance
FOXP3
Forkhead Transcription Factors
hemic and immune systems
Dendritic Cells
Original Articles
Lymphocyte Subsets
Sjogren's Syndrome
030104 developmental biology
medicine.anatomical_structure
Ribonucleoproteins
Interferon Type I
030215 immunology
Subjects
Details
- ISSN :
- 13652249 and 00099104
- Volume :
- 186
- Database :
- OpenAIRE
- Journal :
- Clinical and Experimental Immunology
- Accession number :
- edsair.doi.dedup.....e82c04ee47621f0d1b33b70def4e5d50