CLONAL DELETION OF V-BETA-5-CELLS BY TRANSGENIC I-E RESTRICTED TO THYMIC MEDULLARY EPITHELIUM( T)

A variety of cell types expressing MHC class II molecules is known to function as APC in vitro. We employed the Ig kappa gene enhancer and p romoter to target the class II Ealpha gene, and thereby I-E, exclusive ly to B cells to address their APC function in vivo. Although transgen ic I-E was expressed on B lymphocytes, we unexpectedly obtained I-E on thymic medullary epithelium but not macrophages and at low frequency on dendritic cells. Using these transgenic mice, we constructed bone m arrow irradiation chimeras with I-E expressed only on medullary epithe lium, in order to determine the role of this cell type in tolerance by clonal deletion in the thymus. Although it is accepted that bm-derive d cells play a primary role in deletion, and thymic epithelium can del ete clones to a lesser degree, the role of cortical vs medullary thymi c epithelium has not been directly dissected. We demonstrate that medu llary epithelium alone can tolerize by partial deletion of I-E-reactiv e Vbeta5+ T cells. These results indicate a role for medullary epithel ium in deletion during the later stages of thymic development, and sup port the notion that positive and negative selection of developing T c ells can occur in distinct temporal and anatomic compartments.