Molecular Mechanisms of Growth and Death Control of Hematopoietic Cells by Cytokines

In responding to the challenge of exogenous antigen(s), there is always a dramatic expansion of certain white blood cell populations in order to achieve tasks of self-defense. It is the cytokines secreted by various immunological cells which are responsible for provoking exponential proliferation and differentiation of these blood cells through binding to their own specific cell surface receptors. Not only the rate of proliferation, but also the length of life span of these blood cells increases. Usually some hundred-fold increase of a single cell population can be achieved within several days. However, once the antigen is eliminated from the body, a rapid clearance of these cell types can be expected within several days which returns the hematopoietic cell population to its normal size. This occurs in response to the decrease in the blood concentration of these essential cytokines. Both rapid expansion of desired cell lineage in emergency and rapid elimination of un-warranted cell population after recovery are characteristics of a successful immune response. Interference in the regulation of above mentioned control always results in immune-pathogenesis. Utilizing the factor-dependent cell line as a model system we are interested in the mechanisms of apoptosis initiation by cytokine deprivation, apoptosis suppression by cytokines, and possibly on the mechanisms underlying leukemogenesis.