التفاصيل البيبلوغرافية
| العنوان: |
Critical Role for CD1d-Restricted Invariant NKT Cells in Stimulating Intrahepatic CD8 T-Cell Responses to Liver Antigen. |
| المؤلفون: |
Sprengers, Dave, Sillé, Fenna C.M., Derkow, Katja, Besra, Gurdyal S., Janssen, Harry L.A., Schott, Eckart, Boes, Marianne |
| المصدر: |
Gastroenterology (00165085); Jun2008, Vol. 134 Issue 7, p2132-2143, 12p |
| مصطلحات موضوعية: |
T cells, LYMPHOID tissue, ANTIGENS, LABORATORY mice |
| مستخلص: |
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. [Copyright &y& Elsevier] |
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