Premium
Interleukin‐18 regulates T cell differentiation and the composition of peripheral T cell subsets
Author(s) -
Marleau Annette M.,
Sarvetnick Nora
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.22.1_supplement.669.23
Subject(s) - nod mice , biology , nod , t cell , immunology , thymocyte , microbiology and biotechnology , il 2 receptor , cytokine , peripheral tolerance , autoimmunity , endocrinology , immune system , diabetes mellitus
Interleukin‐18 (IL‐18) has a well‐established role in promoting type 1 cytokine responses in autoimmunity and inflammation. Here, using non‐obese diabetic (NOD) mice that are genetically deficient in IL‐18 (IL‐18KO NOD), we have identified a role for IL‐18 in regulating intra‐thymic T cell differentiation that was associated with constitutive IL‐18 synthesis and IL‐18 receptor expression during thymocyte development. IL‐18 deficiency promoted the survival of double positive thymocytes, thereby permitting increased generation of naïve T cells and enlargement of the peripheral T cell pool. Accordingly, IL‐18KO NOD mice possessed reduced numbers of homeostatically expanding T cells and the periphery displayed the hallmarks of enhanced stability, including reduced steady‐state T cell apoptosis and differentiation of fewer interferon‐gamma producing T cells. These effects were also associated with the presence of fewer effector T cells in the pancreatic lymph nodes and islets and diabetes resistance in IL‐18KO NOD mice. This study defines a previously‐unrecognized role for IL‐18 as a regulator of intra‐thymic T cell differentiation and the peripheral T cell composition, thereby affecting expansion of the niche of potentially autoreactive T cells in NOD mice.