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Cited by 80Chemokine receptors and signalingTransplantation: Methods and OutcomesT-cell and B-cell Immunology

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CXC Chemokine Ligand (CXCL) 9 and CXCL10 Are Antagonistic Costimulation Molecules during the Priming of Alloreactive T Cell Effectors

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Rosenblum, Joshua M, Shimoda, Naohiko, Schenk, Austin D, Zhang, Howard, Kish, Danielle D, Keslar, Karen, Farber, Joshua M, Fairchild, Robert L·2010·The Journal of Immunology
DOI 10.4049/jimmunol.0903831PMC PMC2885704
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Abstract

Donor Ag-reactive CD4 and CD8 T cell production of IFN-gamma is a principal effector mechanism promoting tissue injury during allograft rejection. The CXCR3-binding chemokines CXCL9 and CXCL10 recruit donor-reactive T cells to the allograft, but their role during the priming of donor-reactive T cells to effector function is unknown. Using a murine model of MHC-mismatched cardiac transplantation, we investigated the influence of CXCL9 and CXCL10 during donor-reactive T cell priming. In allograft recipient spleens, CXCL9 and CXCL10 were expressed as early as 24 h posttransplant and increased with similar kinetics, concurrently with CXCR3 expression on T cells. CXCL9, but not CXCL10, expression required NK cell production of IFN-gamma. The absence of CXCL9 in donor allografts, recipients, or both significantly decreased the frequency of donor-reactive CD8 T cells producing IFN-gamma and increased the frequency of donor-reactive CD8 T cells producing IL-17A. In contrast, the absence of CXCL10 increased the frequency of IFN-gamma-producing CD8 T cells in a CXCL9-dependent manner. These data provide novel evidence that donor-reactive CD8 T cells use the CXCR3 chemokine axis as a costimulation pathway during priming to allografts where CXCL9 promotes the development of IFN-gamma-producing CD8 T cells, and CXCL10 antagonizes this skewing.

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Metadata

Authors
Rosenblum, J. M., Shimoda, N., Schenk, A. D., Zhang, H., Kish, D. D., Keslar, K., Farber, J. M., & Fairchild, R. L.
Affiliations
  • Cleveland Clinic (US)
  • Hokkaido University (JP)
  • National Institutes of Health (US)
Corresponding author
Rosenblum, Joshua M
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2010-04-01
Volume
184
Issue
7
Pages
3450-3460
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.0903831
PMC
PMC2885704
OpenAlex
W1786787856
Cited by
80
References
0
Citations by year
2026: 1 · 2025: 3 · 2024: 14 · 2023: 4 · 2022: 4 · 2020: 2 · 2019: 8 · 2018: 6 · 2017: 4 · 2016: 3 · 2015: 3 · 2014: 8 · 2013: 5 · 2012: 7
FWCI
3.17
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (RO1 AI51620, AI40459, T32 GM07250, F30 HL940052)
Topics
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
  • Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
CXCL9, CXCL10, CXCR3, costimulation, T cell priming, allograft rejection, interferon-gamma, IL-17A, natural killer cells, CD8+ T cells, CD4+ T cells, chemokines, alloreactivity
MeSH terms
Animals, Cell Separation, Flow Cytometry, Graft Rejection, Graft Survival, Interferon-gamma, Lymphocyte Activation, Mice, Transgenic, T-Lymphocytes, Transplantation, Homologous, CD4-Positive T-Lymphocytes, Heart Transplantation, CD8-Positive T-Lymphocytes, Reverse Transcriptase Polymerase Chain Reaction, Mice, Chemokine CXCL10, Chemokine CXCL9

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