CD3-EPSILON-MEDIATED SIGNALS RESCUE THE DEVELOPMENT OF CD4+ CD8+ THYMOCYTES IN RAG-2(-/-) MICE IN THE ABSENCE OF TCR BETA-CHAIN EXPRESSION

Recent studies have shown that TCR beta chain expression can effect the differentiation of CD4-CD8- double-negative (DN) thymocytes to CD4+CD8+ double-positive (DP) thymocytes. The TCR beta chain is expressed on the surface of DP thymocytes in association with CD3gamma, delta and epsilon chains, suggesting a potential role for CD3 components in this signaling process. We now report detection of a very low level of surface expression of CD3epsilon on adult DN RAG-2-/- thymocytes. This surface CD3epsilon was associated with CD3gamma and delta chains, as detected by anti-CD3epsilon immunoprecipitation analyses. Significantly, injection of anti-CD3epsilon mAb into RAG-2-/- mice led to the accumulation of an IL-2Ralpha- CD2+ DP cell population and a nearly 100-fold increase in thymic cellularity to essentially normal levels. Together, these data strongly indicate that TCR beta chain-mediated developmental signals are transduced by CD3 components and provide potential insights into mechanisms by which TCR beta chain expression may effect this process.