Induction of chemokine receptor expression during early stages of T cell development

The early events in T lineage commitment are difficult to study because of the rarity of these cells. We have therefore used cloned Pax5-/- pre-BI cell lines as a model system to study this. Stimulation in vitro of Pax5-/- pre-BI cells with stromal cells expressing the Notch ligand Delta-like 1 results in them coincidently undergoing some of the phenotypic and functional changes associated with early T cell commitment. Kinetic analysis indicated that there was a rapid induction of transcripts for the two chemokine receptors CCR4 and CXCR6. Transcripts for CCR8 increased with slower kinetics. Migration assays indicated that Delta-like 1 signalling of Pax5-/- pre-BI cells had induced responsiveness to the chemokines MDC and MIP-1beta, ligands for the receptors CCR4 and CCR8, respectively. Importantly, following Delta-like 1 signalling, similar increases in chemokine receptor transcripts were seen in a recently described bone marrow progenitor subpopulation having significant T cell progenitor activity and being phenotypically and functionally similar to Pax5-/- pre-BI cells. The relevance of these findings to studies of early T cell development will be discussed.