Chapter category: Cytokines/Growth Factors
Ellen V. Rothenberg, Susan B. Ward, Mary A. Yui, Gabriela Hernandez-Hoyos, Fei Chen, Sudipta Bardhan, Robert Chen, Raymond Hotz and Julia A. Yang-Snyder
Chapter authors:
Developmental Specificity of Interleukin2 Expression
The interleukin-2 gene is expressed only by a few types of blood cells and only in acute response to activation. Most of the cells expressing IL2 are T cells, and the most common mode of T-cell stimulation that induces IL2 expression is antigen recognition by the T cell. Although antigen recognition is carried out by T-cell specific receptors, the signaling components downstream of the receptor that actually turn on the IL2 gene do not appear to be T-cell specific. Thus, there are two separate kinds of mechanisms that control IL2 expression: the developmental specificity of IL2 expression is not explained by its activation specificity. This Chapter addresses two questions: what are the molecular barriers that restrict the ability to express IL2 to these cells only? And how are these mechanisms brought into play during the development of these cells from pluripotent precursors?
The ability to express IL2 is heritable: T cells can maintain the ability to express IL2 through tens or hundreds of cycles of proliferation, at least under tissue culture conditions. But T cells are ultimately derived from pluripotent hematopoietic precursors, which give rise to many cell types that do not express IL2. A mechanism must exist to enable the ability to express IL2 to be inherited by T-cell progeny of the stem cell but not by other progeny. This Chapter will survey the status of current evidence on the nature of this mechanism. It should represent either a gain or a loss of function, depending upon whether the pluripotent precursors themselves can express IL2 or not. In any case, this developmental event requires a molecular explanation, either at the level of regulation of critical transcription factors for IL2 or at the level of alterations in the chromatin structure of the IL2 locus itself.
