Background & Aims: Vα14 invariant natural killer T cells (iNKT) are localized in peripheral tissues such as the liver rather than lymphoid tissues. Therefore, their role in modulating the stimulation of conventional, major histocompatibility complex (MHC)-restricted T-cell responses has remained ambiguous. We here describe a role for Vα14 iNKT cells in modulating conventional T-cell responses to antigen expressed in liver, using transferrin-mOVA (Tf-mOVA) mice. Methods: Naïve ovalbumin-specific class I MHC-restricted T cells (OTI) were adoptively transferred into Tf-mOVA mice in the presence or absence of iNKT-cell agonist α-galactosylceramide, after which OTI T-cell priming, antigen-specific cytokine production, cytotoxic killing ability, and liver damage were analyzed. Results: Transfer of OTI cells resulted in robust intrahepatic, antigen-specific proliferation of T cells. OTI T cells were activated in liver, and antigen-specific effector function was stimulated by coactivation of Vα14 iNKT cells using α-galactosylceramide. This stimulation was absent in CD1d-/-Tf-mOVA mice, which lack Vα14 iNKT cells, and was prevented when interferon-γ and tumor necrosis factor-α production by Vα14 iNKT cells was blocked. Conclusions: CD1d-restricted Vα14 iNKT cells stimulate intrahepatic CD8 T-cell effector responses to antigen expressed in liver. Our findings elucidate a previously unknown intervention point for targeted immunotherapy to autoimmune and possibly infectious liver diseases.

Additional Metadata
Persistent URL,
Journal Gastroenterology
Sprengers, D, Sillé, F.C.M, Derkow, K, Besra, G, Janssen, H.L.A, Schott, E, & Boes, M. (2008). Critical Role for CD1d-Restricted Invariant NKT Cells in Stimulating Intrahepatic CD8 T-Cell Responses to Liver Antigen. Gastroenterology, 134(7), 2132–2143. doi:10.1053/j.gastro.2008.02.037