Kerry Casey

E-mail: casey041@umn.edu

Thesis Advisor: Matthew Mescher

Year entered: 2001

Degrees received:
B.S., Medical Microbiology & Immunology, University of Wisconsin-Madison, 2001

Honors and Awards:
• Recipient of MICaB travel award –Fall 2005

Thesis research:
My thesis project has centered on determining the physiological relevance of the known third signal cytokines.  We have previously shown that using artificial antigen presenting cells, that naïve CD8T cells require three signals: antigen, costimulation, and a third signal that can be provided by IL-12 or IFNa in order to become fully activated.  In order to investigate a physiologic role for these cytokines, we proposed a three part approach whereby TCR transgenic and non transgenic naïve CD8 T cells deprived of known third signal cytokines will be assessed for their ability to respond to activating stimuli as provided by 1)characterized peptide and adjuvant systems, 2) purified dendritic cells, or 3)pathogenic challenge.  Through the course of these investigations we identified a new third signal cytokine, IL-21, and work has been done to characterize this third signal so that its relevance may be tested in the above aims. We have characterized the IL-21 third signal and found that it does not require B7 costimulation, functions at even low antigen concentrations and does not work via a STAT 4 or STAT 1 dependent mechanism.  Resulting cells are distinct from effector cells generated with IL-12 or IFNa.  They are highly cytotoxic, do not produce IFNg, can produce TNFa, but do not produce IL-4 or IL-5.  IL-21 as a third signal also partially inhibits IL-12 induced IFNg production.

Publications:

• Casey, K. and M.F. Mescher. 2006 IL-21 Promotes Differentiation of Naïve CD8 T cells to a Unique Effector Phenotype. Manuscript submitted