Regulation of T cell growth
This PhD thesis aims to examine the growth of T cells in response to cytokines of the common gamma chain (yc) family, in particular interleukin (IL)-2 and IL- 15. Cell growth is commonly used to describe cells in exponential division however the growth of a cell is defined by its size and volume, which is directly related to the rate of cell metabolism and protein synthesis. Naive T cells are small and circulate around the body maintaining a minimal rate of metabolic activity and protein synthesis. During an immune response naive T cells undergo rapid proliferation and differentiate into effector cells. These cells produce and secrete large amounts of cytokines and effector molecules allowing them to mediate their immune function. The differentiation of antigen activated T cells to mature effectors takes several days and is regulated by cytokines. These cytokines need to maintain high rates of cell metabolism for a prolonged period. Thus the cytokines that regulate proliferation and differentiation of antigen activated T cells need to sustain cell growth. Data presented in this thesis shows differential roles for gamma chain cytokines, specifically IL-2 and IL-15 in the regulation of protein synthesis and uptake of amino acids, whilst maintaining equal mitogenic capacity. This thesis highlights the possible uncoupling of the rate of cellular division and protein synthesis induced by cytokines and defines a unique role for common gamma chain cytokines in regulation of protein synthesis and ultimately the regulation of cellular function.