Kristin Ness

Ness
  • B.S., Biology, University of Wisconsin-Madison
  • M.S., Pathology, University of Iowa
Date left program: 
09/20/2011
Degree received: 
Ph.D.
Date Ph.D. awarded: 
December, 2011
Research

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 naïve 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

Publications

Ness-Schwickerath KJ, Morita CT. Regulation and function of IL-17A- and IL-22-producing γδ T cells. Cell Mol Life Sci. 2011 Jul;68(14):2371-90. Epub 2011 May 15. Review. PubMed PMID: 21573786; PubMed Central PMCID: PMC3152582.

Ness-Schwickerath KJ, Jin C, Morita CT. Cytokine requirements for the differentiation and expansion of IL-17A- and IL-22-producing human Vgamma2Vdelta2 T cells. J Immunol. 2010 Jun 15;184(12):7268-80. Epub 2010 May 14. PubMed PMID:20483730; PubMed Central PMCID: PMC2965829.

Wheeler DL, Reddig PJ, Ness KJ, Leith CP, Oberley TD, Verma AK. Overexpression of protein kinase C-{epsilon} in the mouse epidermis leads to a spontaneous myeloproliferative-like disease. Am J Pathol. 2005 Jan;166(1):117-26. PubMed PMID: 15632005; PubMed Central PMCID: PMC1602310.

Wheeler DL, Martin KE, Ness KJ, Li Y, Dreckschmidt NE, Wartman M, Ananthaswamy HN, Mitchell DL, Verma AK. Protein kinase C epsilon is an endogenous photosensitizer that enhances ultraviolet radiation-induced cutaneous damage and development of squamous cell carcinomas. Cancer Res. 2004 Nov 1;64(21):7756-65. PubMed PMID: 15520180.

Wheeler DL, Ness KJ, Oberley TD, Verma AK. Protein kinase Cepsilon is linked to 12-O-tetradecanoylphorbol-13-acetate-induced tumor necrosis factor-alpha ectodomain shedding and the development of metastatic squamous cell carcinoma in protein kinase Cepsilon transgenic mice. Cancer Res. 2003 Oct 1;63(19):6547-55. PubMed PMID: 14559850.

Wheeler DL, Ness KJ, Oberley TD, Verma AK. 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. 2003 Jun 15;63(12):3037-42. PubMed PMID: 12810623.

Edsen-Moore MR, Fan J, Ness KJ, Marietta JR, Cook RT, Schlueter AJ. 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 KJ, Fan J, Wilke WW, Coleman RA, Cook RT, Schlueter AJ. 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.

Post-program
Research Assistant
Pathology Research Laboratories
University of Iowa