Th2 cell differentiation from naive <scp>CD</scp>4⁺ T cells is enhanced by autocrine <scp>CC</scp> chemokines in atopic diseases

Abstract

Abstract Background Chemokines are involved not only in regulating leucocyte recruitment, but also in other activities. However, functions other than cell recruitment remain poorly understood. We have already shown that the production of CC chemokine ligand ( CCL )17 and CCL 22 by antigen‐stimulated naïve CD 4 + T cells was higher in asthmatic patients than in healthy controls. However, the role of these chemokines in stimulated naïve CD 4 + T cells remains unclear. Objective To clarify the biological function of CCL 17 and CCL 22 on naïve CD 4 + T, we examined effects of these two chemokines on naïve CD 4 + T cells expressing CC chemokine receptor ( CCR )4 (a receptor for CCL 17 and CCL 22) during differentiation of Th2 cells in asthmatic patients as allergic subjects. Methods Naïve CD 4 + T cells were prepared from healthy controls and patients with asthma. We analysed effect of CCL 17 and CCL 22, and blocking their receptor on differentiation of Th2 cells. Results Production of CCL 17 and CCL 22 by activated naive CD 4 + T cells under Th2 condition was much more in asthmatic patients than in healthy controls. Proliferation and survival of the Th2 differentiating cells and restimulation‐induced IL ‐4 production were much greater in asthmatic patients than in healthy controls. These cell biological phenomena were inhibited by blockade of CCR 4. The biological effects of exogenous CCL 17 and CCL 22 were apparently observed in both healthy controls and asthmatic patients. The effectiveness of these chemokines on naïve CD 4 + T cells from healthy controls was stronger than those from asthmatic patients. We found that thymic stromal lymphopoietin ( TSLP ), a Th2 promoting chemokine, is involved in the activation of CD 4 + naïve T cells via production of CCL 17 and CCL 22. Conclusions and Clinical Relevance These data suggest that CCL 17 and CCL 22 produced by TSLP ‐primed naïve CD 4 + T cells in asthma might contribute to an increase in Th2 cells via autocrine loops.