Natural killer cells in arthritis and chronic inflammation

Description of projects available to graduate students:
Natural killer (NK) cells comprise a significant proportion of joint-infiltrating cells, and their role in the pathogenesis of rheumatoid arthritis (RA) remains to be elucidated. A distinct NK subset, marked by high levels of expression of the CD56 cell surface antigen, has been shown have inflammatory activity. By contrast, a CD56dim NK subset that has poor inflammatory activity is underrepresented in inflamed joints. However, it is unclear whether these two NK subsets represent sequential stages of maturation or different developmental lineages. This is an important issue because different ontogeny may reflect distinct biological functions that influence clinical disease outcomes. Using indelible DNA rearrangements as a clonal marker, we propose to determine the developmental relationship between CD56bright and CD56dim NK. Characterizing the developmental dynamics and functional activities of inflammatory NK cells will provide insights into the development of alternative therapies for RA.

Techniques graduate student will learn:
flow cytometry
single cell PCR, real time PCR
identification of lymphocyte subsets in mouse and man
cell culture
retroviral technology