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.
Maerki
Sarah
S
Developmental and Molecular Immunology, Department of Clinical and Biological Sciences (DKBW), University of Basel, Mattenstrasse 28, CH-4058 Basel, Switzerland.
Ceredig
Rod
R
Rolink
Antonius
A
D019070:Cell Lineage / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000494:pharmacology; D018920:Coculture Techniques; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D009154:Mutation; D051757:PAX5 Transcription Factor / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D014158:Transcription, Genetic; D015854:Up-Regulation
D018925:Chemokines; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D019707:Receptors, Chemokine