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IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking.

IFN-gamma-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-gamma 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-gamma and the IFN-gamma-induced chemokines monokine induced by IFN-gamma (Mig, CXCL9) and IFN-inducible T cell alpha chemoattractant (I-TAC, CXCL11) in the brain, decreased numbers of virus-specific IFN-gamma-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.

Pubmed ID: 11907072

Authors

  • Dufour JH
  • Dziejman M
  • Liu MT
  • Leung JH
  • Lane TE
  • Luster AD

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Data

April 1, 2002

Associated Grants

  • Agency: NIAID NIH HHS, Id: F32AI09716
  • Agency: NCI NIH HHS, Id: F32CA88721
  • Agency: NINDS NIH HHS, Id: NS37336-01
  • Agency: NCI NIH HHS, Id: R0O1CA69212
  • Agency: NINDS NIH HHS, Id: T32NSO74444

Mesh Terms

  • Animals
  • Antigens
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cell Movement
  • Chemokine CXCL10
  • Chemokines, CXC
  • Coronavirus Infections
  • Demyelinating Diseases
  • Dermatitis, Contact
  • Down-Regulation
  • Encephalomyelitis
  • Growth Inhibitors
  • Interferon-gamma
  • Isoantigens
  • Lymphocyte Activation
  • Lymphocyte Culture Test, Mixed
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Murine hepatitis virus
  • Mutagenesis, Site-Directed
  • Ovalbumin
  • Spleen