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CXCR3 expression defines a novel subset of innate CD8 + T cells that enhance immunity against bacterial infection and cancer upon stimulation with IL‐15
Author(s) -
Oghumu Steve,
Terrazas Cesar A.,
Varikuti Sanjay,
Kimble Jennifer,
Vadia Stephen,
Yu Lianbo,
Seveau Stephanie,
Satoskar Abhay R.
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.14-264507
Subject(s) - cxcr3 , innate immune system , cytotoxic t cell , biology , cd8 , population , t cell , immunology , innate lymphoid cell , microbiology and biotechnology , chemokine , immune system , chemokine receptor , medicine , in vitro , biochemistry , environmental health
Innate CD8 + T cells are a heterogeneous population with developmental pathways distinct from conventional CD8 + T cells. However, their biology, classification, and functions remain incompletely understood. We recently demonstrated the existence of a novel population of chemokine (C‐X‐C motif) receptor 3 (CXCR3)‐positive innate CD8 + T cells. Here, we investigated the functional properties of this subset and identified effector molecules and pathways which mediate their function. Adoptive transfer of IL‐15 activated CXCR3 + innate CD8 + T cells conferred increased protection against Listeria monocytogenes infection in susceptible IFN‐γ –/– mice compared with similarly activated CXCR3 – subset. This was associated with enhanced proliferation and IFN‐γ production in CXCR3 + cells. Further, CXCR3 + innate cells showed enhanced cytotoxicity against a tumor cell line in vitro. In depth analysis of the CXCR3 + subset showed increased gene expression of Ccl5, Klrc1, CtsW, GP49a, IL‐2Rβ, Atp5e , and Ly6c but reduced IFN‐γR2 and Art2b. Ingenuity pathway analysis revealed an up‐regulation of genes associated with T‐cell activation, proliferation, cytotoxicity, and translational initiation in CXCR3 + populations. Our results demonstrate that CXCR3 expression in innate CD8 + T cells defines a subset with enhanced cytotoxic potential and protective antibacterial immune functions. Immunotherapeutic approaches against infectious disease and cancer could utilize CXCR3 + innate CD8 + T‐cell populations as novel clinical intervention strategies.—Oghumu, S., Terrazas, C. A., Varikuti, S., Kimble, J., Vadia, S., Yu, L., Seveau, S., Satoskar, A. R., CXCR3 expression defines a novel subset of innate CD8+ T cells that enhance immunity against bacterial infection and cancer upon stimulation with IL‐15. FASEB J. 29, 1019–1028 (2015). www.fasebj.org