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

J Immunol. 2002 Apr 1;168(7):3195-204. doi: 10.4049/jimmunol.168.7.3195.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens / pharmacology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Movement / genetics*
  • Cell Movement / immunology*
  • Chemokine CXCL10
  • Chemokines, CXC / deficiency*
  • Chemokines, CXC / genetics
  • Chemokines, CXC / physiology*
  • Coronavirus Infections / genetics
  • Coronavirus Infections / immunology
  • Demyelinating Diseases / genetics
  • Demyelinating Diseases / immunology
  • Demyelinating Diseases / prevention & control
  • Demyelinating Diseases / virology
  • Dermatitis, Contact / genetics
  • Dermatitis, Contact / prevention & control
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • Encephalomyelitis / genetics
  • Encephalomyelitis / immunology
  • Growth Inhibitors / pharmacology
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / metabolism
  • Isoantigens / immunology
  • Lymphocyte Activation / genetics*
  • Lymphocyte Activation / immunology
  • Lymphocyte Culture Test, Mixed
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Murine hepatitis virus / immunology
  • Mutagenesis, Site-Directed
  • Ovalbumin / immunology
  • Ovalbumin / pharmacology
  • Spleen / immunology
  • Spleen / pathology


  • Antigens
  • Chemokine CXCL10
  • Chemokines, CXC
  • Growth Inhibitors
  • Isoantigens
  • Interferon-gamma
  • Ovalbumin