IFN-γ-Inducible Protein 10 (IP-10; CXCL10)-Deficient Mice Reveal a Role for IP-10 in Effector T Cell Generation and Trafficking

Dufour, Jennifer H; Dziejman, Michelle; Liu, Michael T; Leung, Josephine H; Lane, Thomas E; Luster, Andrew D

doi:10.4049/jimmunol.168.7.3195

Cited by 1,075Chemokine receptors and signalinginterferon and immune responsesT-cell and B-cell Immunology

IFN-γ-Inducible Protein 10 (IP-10; CXCL10)-Deficient Mice Reveal a Role for IP-10 in Effector T Cell Generation and Trafficking

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Dufour, Jennifer H, Dziejman, Michelle, Liu, Michael T, Leung, Josephine H, Lane, Thomas E, Luster, Andrew D·2002·The Journal of Immunology

DOI 10.4049/jimmunol.168.7.3195

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Abstract

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.

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CXCL10 attracts T cells, NK cells, and dendritic cells.
“It serves to attract T cells, NK cells, dendritic cells (84), and also has potent anti-cancer activity.”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [84]
CXCL10 has been shown to promote effector T cell generation and function.
“Additionally, CXCL10 has been shown to promote effector T cell generation and function56,57.”
From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [56]
CXCL10 (IP-10) is secreted in response to IFNγ.
“CXCL10 (aka IFNγ-induced protein 10/IP-10) is secreted in response.”
From Secondary bacterial infections associated with influenza pandemics (2017) · cites this paper as Dufour et al., 2002
IP-10 attracts various immune cells including activated T cells, monocytes and macrophages, causing inflammation.
“IP-10 attracts various immune cells including activated T cells, monocytes and macrophages, therefore causing inflammation (Dufour et al., 2002; Hoffmann et al., 2016).”
From Secondary bacterial infections associated with influenza pandemics (2017) · cites this paper as Dufour et al., 2002

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Authors: Dufour, J. H., Dziejman, M., Liu, M. T., Leung, J. H., Lane, T. E., & Luster, A. D.
Affiliations: Harvard University (US)
University of California, Irvine (US)
Corresponding author: Dziejman, Michelle
ORCID: Dziejman, Michelle
Lane, Thomas E
Luster, Andrew D
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2002-04-01
Volume: 168
Issue: 7
Pages: 3195-3204
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.168.7.3195
OpenAlex: W2129071472
Cited by: 1,075
References: 74
Citations by year: 2026: 22 · 2025: 39 · 2024: 54 · 2023: 41 · 2022: 58 · 2021: 53 · 2020: 45 · 2019: 48 · 2018: 49 · 2017: 62 · 2016: 60 · 2015: 65 · 2014: 63 · 2013: 46 · 2012: 45
FWCI: 16.17
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: Multiple Sclerosis Society
National Institutes of Health (7r29ns037336-02, 5f32ai009716-02)
National Cancer Institute (F32CA088721, R0O1CA69212, F32-CA88721)
National Institute of Allergy and Infectious Diseases (F32AI09716)
National Institute of Neurological Disorders and Stroke (NS37336-01, T32NSO74444)
Topics: Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: CXCL10, chemokines, T cell migration, contact hypersensitivity, T cell proliferation, interferon-gamma, demyelination, Th1 inflammation, CXCL9, CXCL11, CD4+ T cells, CD8+ T cells, viral encephalitis
MeSH terms: Animals, Antigens, Cell Movement, Demyelinating Diseases, Dermatitis, Contact, Encephalomyelitis, Growth Inhibitors, Murine hepatitis virus, Interferon-gamma, Isoantigens, Lymphocyte Culture Test, Mixed, Lymphocyte Depletion, Lymphocyte Activation, Mice, Inbred BALB C, Mice, Inbred C57BL, Ovalbumin, Spleen, CD4-Positive T-Lymphocytes, Down-Regulation, Mutagenesis, Site-Directed, Mice, Knockout, Coronavirus Infections, CD8-Positive T-Lymphocytes, Chemokines, CXC, Mice, Chemokine CXCL10

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IFN-γ-Inducible Protein 10 (IP-10; CXCL10)-Deficient Mice Reveal a Role for IP-10 in Effector T Cell Generation and Trafficking

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