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PD‐1 negatively regulates CD8 T cell‐mediated mucosal autoimmunity
Author(s) -
Vezys Vaiva,
Masopust David,
Sharpe Arlene,
Freeman Gordon,
Newell Kenneth,
Ahmed Rafi
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.852.4
Subject(s) - autoimmunity , immunology , t cell , cd8 , biology , antigen , immune system
Loss of T cell tolerance to mucosal self‐antigens can lead to debilitating diseases, such as inflammatory bowel disease. We wished to identify the developmental cues that discriminate between T cell tolerance induction vs. autoreactivity within the intestine. Some evidence suggests that signaling through the programmed death (PD) pathway may augment intestinal T cell responses, whereas responses to non‐mucosal proteins are oppositely affected. We assessed the role of PD‐1 and PD‐L1 in CD8 T cell‐mediated intestinal autoimmunity. Upon transfer of naive OT‐I cells to mice producing OVA exclusively within small intestinal epithelial cells, T cells expand in lymph nodes and migrate to the intestine, but cause no pathology, despite large numbers of cells within the antigen‐bearing tissue. With the inclusion of a blocking antibody to PD‐L1, OT‐I cell numbers and function increased dramatically and led to fatal autoimmunity, similar to disease induced with the inclusion of inflammatory agents. Therefore, PD‐1 signaling can be a critical regulator of tolerogenic vs. pathological responses. These results highlight the importance of negative regulatory mechanisms in preventing mucosal autoimmunity.