Kristin Ness |
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| Research Interests | |
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Among the non-conventional T cells, γδ T cells represent a sizeable population of innate-like T cells which bridge the gap between innate and adaptive immunity. Much like αβ T cells (CD4 and CD8), γδ T cells exhibit antigen specificity, robustly proliferate in response to activation, produce pro-inflammatory cytokines (such as TNFα and IFN-γ) and are highly cytolytic to their targets. Vγ2Vδ2 γδ T cells (the major subset of human peripheral blood γδ) are unique from αβ T cells and mouse γδ T cells in that they recognize as antigen, metabolites common to microbes and cancerous cells.
It has been shown that γδ T cells in mice are potent IL-17 producers, and in different disease models (in mice), γδ T cells constitute a greater fraction of IL-17 producing cells and secrete IL-17 earlier in disease than conventional CD4 αβ (Th17) T cells. IL-17 is a family (IL-17A through IL-17F) of pro-inflammatory cytokines important in a diverse array of functions ranging from neutrophil recruitment to induction of wound repair and tissue remodeling. Excessive or inappropriate IL-17 production by T cells is thought to contribute to the etiology of rheumatoid arthritis, Crohn's disease, ulcerative colitis, multiple sclerosis and lupus. However, appropriate IL-17 production by T cells is protective in response to bacterial infections and in the prevention of cancer. We have found that naive Vγ2Vδ2 T cells (present in umbilical cord blood) can be polarized into Th17-like cells, characterized by high IL-17 production and absent IL-22 and IFN-γ production (we refer to as "Tγδ17" T cells). Their polarization requires similar cytokine conditions as that of Th17 αβ T cells. In addition, we have identified populations of memory Vγ2Vδ2 T cells, a IL-17A and IFN-γ dual producing population ("Tγδ 1/17" Vγ2Vδ2 T cells) and an IL-22 producing population ("Tγδ22" Vγ2Vδ2 T cells) which both exist at low levels in the blood of healthy human donors. Our future goals are to further characterize these Vγ2Vδ2 T cell populations and to study their occurrence in various human disease settings. In addition, we plan to study their function in a bacterial infection model using non-human primates |
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| Publications | |
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Wheeler, D. L., Ness , K. J., Oberley, T. D. & Verma, A. K. Proteinkinase C epsilon is linked to 12-Otetradecanoylphorbol- 13-acetate-induced tumor necrosis factor-alpha ectodomain shedding and the development of metastatic squamous cell carcinoma in protein kinase C epsilon transgenic mice. Cancer Res 63, 6547-55, 2003.
Wheeler, D. L., Ness , K. J., Oberley, T. D. & Verma, A. K. Inhibition of the development of metastatic squamous cell carcinoma in protein kinase C epsilon transgenic mice by alpha-difluoromethylornithine accompanied by marked hair follicle degeneration and hair loss. Cancer Res 63, 3037-42, 2003. Wheeler, D. L., Martin, K. E., Ness , K. J., et al. Protein kinase C epsilon is an endogenous photosensitizer that enhanses ultraviolet radiation-induced cutaneous damage and development of squamous cell carcinomas. Cancer Res 64, 7756-65, 2004. Wheeler, D. L., Reddig, P. J., Ness , K. J., et al. Overexpression of protein kinase C & in the mouse epidermis leads to a spontaneous myeloproliferative-like disease. Am J Pathol 166, 117-26, 2005. Edsen-Moore, M.R., Fan, J., Ness , K.J., Marietta, J.R., Cook, R.T., and Schlueter, A.J. Effects of chronic ethanol feeding on murine dendritic cell numbers, turnover rate, and dendropoiesis. Alcohol Clin Exp Res. 2008 Jul;32(7):1309-20. PubMed PMID: 18540909; PubMed Central PMCID: PMC2553395. Ness , K.J., Fan, J., Wilke, W.W., Coleman, R.A., Cook, R.T., and Schlueter, A.J. Chronic ethanol consumption decreases murine Langerhans cell numbers and delays migration of Langerhans cells as well as dermal dendritic cells. Alcohol Clin Exp Res. 2008 Apr;32(4):657-68. Epub 2008 Jan 28. PubMed PMID: 18241312; PubMed Central PMCID: PMC2276693. |
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