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Regulation of Antiviral Immunity Synergistically Controls Autoimmunity in Type 1 Diabetes
Author(s) -
Filippi Christophe M,
Estes Elizabeth A,
Oldham Janine E,
Larsson Par,
Wolfe Tom,
Herrath Matthias G
Publication year - 2009
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.23.1_supplement.930.3
Subject(s) - immunology , foxp3 , autoimmunity , il 2 receptor , lymphocytic choriomeningitis , immune system , nod mice , nod , autoimmune disease , type 1 diabetes , regulatory t cell , biology , immunity , medicine , cd8 , diabetes mellitus , t cell , antibody , endocrinology
While the inflammatory immune response mounted against viral infections is usually believed to enhance autoimmune processes, we discovered that it triggers two key regulatory phenomena that synergize to promote tolerance in type 1 diabetes (T1D). Acute infection of prediabetic non‐obese diabetic (NOD) mice with lymphocytic choriomeningitis virus (LCMV) significantly delayed autoimmune diabetes and reduced disease incidence. The delay of T1D was due to transient up‐regulation of Programmed death‐ligand 1 (PD‐L1) which was induced, at least in part, by interferon, and caused the elimination of PD‐1‐expressing, diabetogenic CD8 + T cells. The reduction of T1D incidence was due to increased number and function of CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) which produced TGF‐β and maintained long‐term tolerance. PD‐L1 and virally enhanced Tregs conferred marked protection from T1D by acting together in synergy. LCMV induced the regulatory mechanisms that prevented T1D by utilizing Toll‐like receptor 2 and dendritic cells. These results reconcile current discordance about the role of viruses in T1D and provide novel insight into disease etiology and potential treatment.