| First Author | Sprengers D | Year | 2008 |
| Journal | Gastroenterology | Volume | 134 |
| Issue | 7 | Pages | 2132-43 |
| PubMed ID | 18549881 | Mgi Jnum | J:137194 |
| Mgi Id | MGI:3798319 | Doi | 10.1053/j.gastro.2008.02.037 |
| Citation | Sprengers D, et al. (2008) Critical role for CD1d-restricted invariant NKT cells in stimulating intrahepatic CD8 T-cell responses to liver antigen. Gastroenterology 134(7):2132-43 |
| abstractText | BACKGROUND & AIMS: V alpha14 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 V alpha14 iNKT cells in modulating conventional T-cell responses to antigen expressed in liver, using transferrin-mOVA (Tf-mOVA) mice. METHODS: Naive 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 alpha-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 Valpha14 iNKT cells using alpha-galactosylceramide. This stimulation was absent in CD1d(-/-)Tf-mOVA mice, which lack V alpha14 iNKT cells, and was prevented when interferon-gamma and tumor necrosis factor-alpha production by V alpha14 iNKT cells was blocked. CONCLUSIONS: CD1d-restricted V alpha14 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. |
