Premium
Antigen presentation by lymph node stroma: Potential for tolerogenic immunotherapy
Author(s) -
Collier Airis Yonekura,
Reynoso Erika,
Tjota Melissa,
Turley Shan J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.474
Subject(s) - antigen , immune tolerance , cd80 , antigen presentation , t cell , immunology , microbiology and biotechnology , central tolerance , antigen presenting cell , immune system , foxp3 , cytotoxic t cell , major histocompatibility complex , biology , chemistry , cd40 , in vitro , biochemistry
Developing T cells that recognize self‐antigen undergo negative selection mediated by medullary thymic epithelial cells (mTECs) and dendritic cells (DCs) in the thymus. Self‐reactive T cells escaping central tolerance were thought to be regulated peripherally only by DCs. Our lab recently described a novel lymph node stroma cell (LNSC) capable of inducing antigen‐specific T cell deletional tolerance. LNSCs mediate tolerance through expression of peripheral tissue antigens, similarly to mTECs. To better characterize LNSCs we developed a system to expand LNSCs in vitro . LNSC express MHC class I and II, and costimulatory molecules, CD80 and PD‐L1, enabling LNSC to interface with and modulate T cell responses in an antigen‐specific manner. LNSC take up antigen for cross‐presentation to CD8 + T cells, inducing proliferation. Preliminary data show that LNSC pulsed with MHCII‐restricted peptide induce FOXP3 expression in naïve CD4 + T cells, suggesting LNSC induce Treg differentiation. Because DCs transition from tolerance inducers to potent immune activators in response to inflammation, their use in tolerogenic vaccines presents issues of clinical safety. By contrast, LNSCs do not undergo this transformation and may prove safer for therapy. We will test the efficacy of LNSCs in reinforcing tolerance in vivo. LNSCs have the potential for use as therapy in graft rejection or autoimmune disease like type 1 diabetes.