COMMITMENT OF IMMATURE CD4(-CELL RECEPTOR (TCR) CHAINS()8(+) THYMOCYTES TO THE CD4 LINEAGE REQUIRES CD3 SIGNALING BUT DOES NOT REQUIRE EXPRESSION OF CLONOTYPIC T)

As a consequence of positive selection in the thymus, immature CD4(+)8 (+) double-positive, [DP] thymocytes selectively terminate synthesis o f one coreceptor molecule and, as a result, differentiate into either CD4(+) or CD8(+) T cells. The decision by individual DP thymocytes to terminate synthesis of one or the other coreceptor molecule is referre d to as lineage commitment. Previously, we reported that the intrathym ic signals that induced commitment to the CD4 versus CD8 T cell lineag es were markedly asymmetric. Notably, CD8 commitment appeared to requi re lineage-specific signals, whereas CD4 commitment appeared to occur in the absence of lineage-specific signals by default. Consequently, i t was unclear whether CD4 commitment, as revealed by selective termina tion of CD8 coreceptor synthesis, occurred in all DP thymocytes, or wh ether CD4 commitment occurred only in T cell receptor (TCR)-CD3-signal ed DP thymocytes. Here, we report that selective termination of CD8 co receptor synthesis does not occur in DP thymocytes spontaneously. Rath er, CD4 commitment in DP thymocytes requires signals transduced by eit her CD3 or zeta chains, which can signal CD4 commitment even in the ab sence of clonotypic TCR chains.