IL-4-expressing bronchoalveolar T cells from asthmatic and healthy subjects preferentially express CCR3 and CCR4

Background: The concept of the polarization of chemokine receptor expression by T(H)1 and T(H)2 cells provides an attractive mechanism for their differential recruitment to tissue, which could be subject to disease-specific therapeutic intervention. The paradigm that T(H)1 cells preferentially express CXCR3 and CCR5 and T(H)2 cells preferentially express CCR3, CCR4, and CCR8 has been well established in the setting of in vitro polarized cell lines; however, the situation in vivo appears less clear-cut. Objective: We sought to investigate whether this pattern of polarization can be demonstrated in human lung tissue. Methods: We used single-cell analysis to investigate the relationship between chemokine receptor expression and cytokine production on peripheral blood and bronchoalveolar lavage fluid T cells in patients with asthma, a putative T(H)2 disease, as well as in healthy control subjects. Results: We have found in both asthmatic and control subjects that IL-4-expressing blood and bronchoalveolar lavage fluid T cells are significantly more likely to express the T(H)2 type 2 chemokine receptors CCR3 and CCR4, with 10-fold and 2-fold differences in expression, respectively, compared with IFN-gamma-expressing cells. Conclusion: We have provided evidence that polarization of T(H)2-type chemokine receptors on IL-4-expressing cells can be demonstrated in an in vivo setting and therefore that these cells might indeed be susceptible to differential patterns of recruitment as a result of expression of the relevant chemokines at inflammatory sites.