Environmental influence on T cell receptor α gene rearrangement and expression in vitro

Publisher Website
Google Scholar
Abstract
Experiments were designed to test whether T cell progenitors are committed to particular T cell receptor (TcR) gene rearrangement and expression patterns (prior to rearrangement) or whether such patterns are molded by the thymic microenvironment in which T cells develop. To this end, day 14 fetal thymocytes were removed from their normal environment and grown in organ culture (FTOC) for 5 to 12 days. RNA was extracted from organ‐cultured cells, processed to cDNA, and TcR α sequences were amplified by the polymerase chain reaction for cloning and sequening. By the examination of N‐region additions and V‐gene usage, and by the comparison of resultant patterns with those of early vs. adult stages of T cell differentiation in vivo, it was demonstrated that thymocytes in FTOC did not maintain early patterns of gene rearrangement. The thymocyte patterns were most dissimilar from those of normal, early ontogeny when interleukin‐4 was added to FTOC. Taken together, results demonstrated the flexibility of T cell progenitors and that environment plays a critical role in the molding of TcR α rearrangement and expression patterns.