IFN-γ-Inducible Protein 10 (IP-10; CXCL10)-Deficient Mice Reveal a Role for IP-10 in Effector T Cell Generation and Trafficking
Autor: | Jennifer H. Dufour, Josephine H. Leung, Thomas E. Lane, Michael T. Liu, Michelle Dziejman, Andrew D. Luster |
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Rok vydání: | 2002 |
Předmět: |
CD4-Positive T-Lymphocytes
Isoantigens Chemokine Ovalbumin T cell Immunology Down-Regulation CD8-Positive T-Lymphocytes Biology Dermatitis Contact Lymphocyte Activation Lymphocyte Depletion Interferon-gamma Mice Antigen Cell Movement medicine Animals Immunology and Allergy CXCL10 Cytotoxic T cell CXCL11 Antigens Encephalomyelitis Mice Knockout Mice Inbred BALB C Murine hepatitis virus Molecular biology Growth Inhibitors Chemokine CXCL10 Mice Inbred C57BL medicine.anatomical_structure Mutagenesis Site-Directed biology.protein CXCL9 Lymphocyte Culture Test Mixed Coronavirus Infections Chemokines CXC Spleen CD8 Demyelinating Diseases |
Zdroj: | The Journal of Immunology. 168:3195-3204 |
ISSN: | 1550-6606 0022-1767 |
Popis: | IFN-γ-inducible protein 10 (IP-10, CXCL10), a chemokine secreted from cells stimulated with type I and II IFNs and LPS, is a chemoattractant for activated T cells. Expression of IP-10 is seen in many Th1-type inflammatory diseases, where it is thought to play an important role in recruiting activated T cells into sites of tissue inflammation. To determine the in vivo function of IP-10, we constructed an IP-10-deficient mouse (IP-10−/−) by targeted gene disruption. Immunological analysis revealed that IP-10−/− mice had impaired T cell responses. T cell proliferation to allogeneic and antigenic stimulation and IFN-γ secretion in response to antigenic challenge were impaired in IP-10−/− mice. In addition, IP-10−/− mice exhibited an impaired contact hypersensitivity response, characterized by decreased ear swelling and reduced inflammatory cell infiltrates. T cells recovered from draining lymph nodes also had a decreased proliferative response to Ag restimulation. Furthermore, IP-10−/− mice infected with a neurotropic mouse hepatitis virus had an impaired ability to control viral replication in the brain. This was associated with decreased recruitment of CD4+ and CD8+ lymphocytes into the brain, reduced levels of IFN-γ and the IFN-γ-induced chemokines monokine induced by IFN-γ (Mig, CXCL9) and IFN-inducible T cell α chemoattractant (I-TAC, CXCL11) in the brain, decreased numbers of virus-specific IFN-γ-secreting CD8+ cells in the spleen, and reduced levels of demyelination in the CNS. Taken together, our data suggest a role for IP-10 in both effector T cell generation and trafficking in vivo. |
Databáze: | OpenAIRE |
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