The Transient Expression of C-C Chemokine Receptor 8 in Thymus Identifies a Thymus Indentifies a Thymocyte Subset Committed to Become CD4~+ Single-Positive T Cells

摘要

'eveloping T cells journey through the different thymic microenvironments while receiving signals that eventually will allow some f them to become mature naive T cells exported to the periphery. This maturation can be visualized by the phenotype of the eveloping cells. CCR8 is a IJ-chemokine receptor preferentially expressed in the thymus. We have developed 8F4, an anti-mouse ;CR8 mAb that is able to neutralize the ligand-induced activation of CCR8, and used it to characterize the CCR8 protein ~pression in the dilferent thymocyte subsets. Taking into account the intrathymic lineage relationships, our data showed that ;CR8 expression in thymus followed two transient waves along T cell maturation. The first one took place in CD4- CD8- ouble-negative thymocytes, which showed a low CCR8 expression, and the second wave occurred after TCR activation by the ,g-dependent positive selection in CD4+ CD8+ double-positive cells. From that maturation stage, CCR8 expression gradually .1creased as the CD4+ cell dilferentiation proceeded, reaching a maximum at the CD4+ CD8- single-positive stage. These CD4+ ells expressing CCR8 were also CD69high CD62L low thymocytes, suggesting that they still needed to undergo some dilferentiation tep before becoming functionally competent naive T cells ready to be exported from the thymus. Interestingly, no significant mounts of CCR8 protein were detectable in CD4- CD8+ thymocytes. Our data showing a clear regulation of the CCR8 protein .1 thymus suggest a relevant role for CCR8 in this lymphoid organ, and identify CCR8 as a possible marker of thymocyte subsets ecently committed to the CD4+ lineage.