The transient expression of C-C chemokine receptor 8 in thymus identifies a thymocyte subset committed to become CD4(+) single-positive T cells

Developing T cells journey through the different thymic microenvironments w hile receiving signals that eventually will allow some of them to become ma ture naive T cells exported to the periphery, This maturation can be visual ized by the phenotype of the developing cells. CCR8 is a beta -chemokine re ceptor preferentially expressed in the thymus, We have developed 8F4, an an ti-mouse CCR8 mAb that is able to neutralize the ligand-induced activation of CCR8, and used it to characterize the CCR8 protein expression in the dif ferent thymocyte subsets, Taking into account the intrathymic lineage relat ionships, our data showed that CCR8 expression in thymus followed two trans ient waves along T cell maturation. The first one took place in CD4(-) CD8( -) double-negative thymocytes, which showed a low CCR8 expression, and the second wave occurred after TCR activation by the Ag-dependent positive sele ction in CD4(+) CD8(+) double-positive cells. From that maturation stage, C CR8 expression gradually increased as the CD4(+) cell differentiation proce eded, reaching a maximum at the CD4(+) CD8(-) single-positive stage, These CD4(+) cells expressing CCR8 were also CD69(high) CD62L(low) thymocytes, su ggesting that they still needed to undergo some differentiation step before becoming functionally competent naive T cells ready to be exported from th e thymus, Interestingly, no significant amounts of CCR8 protein were detect able in CD4(-) CD8(+) thymocytes, Our data showing a clear regulation of th e CCR8 protein in thymus suggest a relevant role for CCR8 in this lymphoid organ, and identify CCR8 as a possible marker of thymocyte subsets recently committed to the CD4(+) lineage.