CCR4 was cloned in 1995 from a human immature basophilic cell line KU812. and was initially identified as a receptor for MIP-lo. RANTES. and MCP-1 following overexpression in Xenopus oocytes and IIL-60 cells. Subsequently. CCR4 was shown to be a high-affinity receptor for thymus and activation regulated chemokine (TARC) and macrophage-derived chemo-kine (MDC). CCR4 mRNA is found in thymus, spleen, and in peripheral blood leukocyte populations, notably activated CD4 I T cells, monocytes, and to a lesser extent on basophils. CCR4 mRNA is also highly expressed on human platelets.
CCR4 is the major chemokine receptor functionally expressed on in vitro polarized TH2 T cells, suggesting that this receptor, and its ligands. may play an important role in the development of the TH2 phenolype. as well as in the homing of T cells to sites of inflammation in TH2-type diseases. A recent report has shown that CCR4 is also expressed on all skin-homing T cells expressing cutaneous lymphocyte antigen (CLA). The tissue distribution of CCR4 in mice is similar to that found in humans. However, the expression of CCR4 on specific mouse cell populations can only be inferred from the response of isolated cells to the known CCR4 ligands in assays such as chemotaxis. as antimouse CCR4 antibodies are not yet generally available.
As such, CCR4 has been postulated to play a role in thymic maturation due to the restricted response of CD4I /CD8I (double-positive) T cells to the CCR4 ligand MDC. As in humans. CCR4 is also expressed on in v/Vro-derived mouse TH2 T cells. A preliminary report on targeted deletion of the CCR4 gene in mice has now appeared in the literature. This report indicates that CCR4-deficienl mice are phenotypically normal in the unstressed state and that the deletion of CCR4 had no effect on the development of the immune response in a classical TH2-dependenl model of airway inflammation. Further studies with Uiis animal model and with anli-CCR4 monoclonal antibodies should help to elucidate the role of CCR4 in immunity, inflammation, and other biological functions.