CC-chemokine receptor 6 is expressed on diverse memory subsets of T cells and determines responsiveness to macrophage inflammatory protein 3 alpha

CC-chemokine receptor (CCR) 6 is the only known receptor for macrophage inf lammatory protein (MIP)-3 alpha, a CC chemokine chemotactic for lymphocytes and dendritic cells, Using anti-serum that we raised against the N-termina l residues of CCR6, we have characterized the surface expression of CCR6 on peripheral blood leukocytes and we have correlated CCR6 expression with re sponses to MIP-3 alpha. We found that CCR6 was expressed only on memory T c ells, including most alpha(4)beta(7) memory cells and cutaneous lymphocyte- associated Ag-expressing cells, and on B cells, Accordingly, chemotaxis of T cells to MIP-3 alpha was limited to memory cells. Moreover, calcium signa ls on T cells in response to MIP-3 alpha were confined to CCR6-expressing c ells, consistent with CCR6 being the only MIP-3 alpha receptor on periphera l blood T cells. Unlike many CC chemokines, MIP-3 alpha produced a calcium signal on freshly isolated T cells, and CCR6 expression was not increased b y up to 5 days of treatment with IL-2 or by cross-linking CD3. Despite thei r surface expression of CCR6, freshly isolated B cells did not respond to M IP-3 alpha. In addition to staining peripheral blood leukocytes, our anti-s erum detected CCR6 on CD34(+) bone marrow cell-derived dendritic cells, Our data are the first to analyze surface expression of CCR6, demonstrating re ceptor expression on differentiated, resting memory T cells, indicating dif ferences in receptor signaling on T cells and B cells and suggesting that C CR6 and MIP-3 alpha may play a role in the physiology of resting memory T c ells and in the interactions of memory T cells, B cells, and dendritic cell s.