| First Author | Oghumu S | Year | 2015 |
| Journal | FASEB J | Volume | 29 |
| Issue | 3 | Pages | 1019-28 |
| PubMed ID | 25466888 | Mgi Jnum | J:219639 |
| Mgi Id | MGI:5629444 | Doi | 10.1096/fj.14-264507 |
| Citation | Oghumu S, et al. (2015) 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(3):1019-28 |
| abstractText | 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-gamma(-/-) mice compared with similarly activated CXCR3(-) subset. This was associated with enhanced proliferation and IFN-gamma 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-2Rbeta, Atp5e, and Ly6c but reduced IFN-gammaR2 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. |
