Aberrant in vivo T helper type 2 cell response and impaired eosinophil recruitment in CC chemokine receptor 8 knockout mice

Chemokine receptors transduce signals important for the function and traffi cking of leukocytes. Recently, it has been shown that CC chemokine receptor (CCR)8 is selectively expressed by Th2 subsets, but its functional relevan ce is unclear. To address the biological role of CCR8, we generated CCR8 de ficient (-/-) mice. Here we report defective T helper type 2 (Th2) immune r esponses in vivo in CCR8(-/-) mice in models of Schistosomaa mansoni solubl e egg antigen (SEA)-induced granuloma formation as well as ovalbumin (OVA)- and cockroach antigen (CRA)-induced allergic airway inflammation. In these mice, the response to SEA, OVA, and CRA showed impaired Th2 cytokine produ ction that was associated with aberrant type 2 inflammation displaying a 50 to 80% reduction in eosinophils. In contrast, a prototypical Th1 immune re sponse, elicited by Mycobacteria bovis purified protein derivative (PPD) wa s unaffected by CCR8 deficiency. Mechanistic analyses indicated that Th2 ce lls developed normally and that the reduction in eosinophil recruitment was likely due to systemic reduction in interleukin 5. These results indicate an important role for CCR8 in Th2 functional responses in vivo.