CC chemokine receptor (CCR)3/eotaxin is followed by CCR4/monocyte-derived chemokine in mediating pulmonary T helper lymphocyte type 2 recruitment after serial antigen challenge in vivo

Isolated peripheral blood CD4 cells front allergic individuals express CC c hemokine receptor (CCR)3 and CCR4 after expansion in vitro. In addition, hu man T helper type 2 (Th2) cells polarized in vitro selectively express CCR3 and CCR4 at certain stages of activation/differentiation and respond prefe rentially to the ligands:eotaxin and monocyte-derived chemokine (MDC). Howe ver, controversy arises when the in vivo significance of this distinct expr ession is discussed. To address the functional role of CCR3/eotaxin and CCR 4/MDC during the in vivo recruit ment of Th2 cells, we have transferred eff ector Th cells into naive mice to induce allergic airway disease. Tracking of these cells after repeated antigen challenge has established that both C CR3/eotaxin and CCR4/MDC axes contribute to the recruitment of Th2 cells to the lung, demonstrating the in vivo relevance of the expression of these r eceptors on Th2 cells. We have shown that involvement of the CCR3/eotaxin p athway is confined to tarry stages of the response in vivo, whereas repeate d antigen stimulation results in the predominant use of the CCR4/MDC pathwa y. We propose that effector Th2 cells respond to both CCR3/eotaxin and CCR4 /MDC pathways initially, but that a progressive increase in CCR4-positive c ells results in the predominance of the CCR4/MDC axis in the long-term recr uitment of Th2 cells in vivo.