Th2 cell differentiation from naive CD4⁺ T cells is enhanced by autocrine CC chemokines in atopic diseases

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 CCL22 by antigen-stimulated naïve CD4⁺  T cells was higher in asthmatic patients than in healthy controls. However, the role of these chemokines in stimulated naïve CD4⁺ T cells remains unclear.

To clarify the biological function of CCL17 and CCL22 on naïve CD4⁺ T, we examined effects of these two chemokines on naïve CD4⁺ T cells expressing CC chemokine receptor (CCR)4 (a receptor for CCL17 and CCL22) during differentiation of Th2 cells in asthmatic patients as allergic subjects.

Naïve CD4⁺ T cells were prepared from healthy controls and patients with asthma. We analysed effect of CCL17 and CCL22, and blocking their receptor on differentiation of Th2 cells.

Production of CCL17 and CCL22 by activated naive CD4⁺ 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 CCR4. The biological effects of exogenous CCL17 and CCL22 were apparently observed in both healthy controls and asthmatic patients. The effectiveness of these chemokines on naïve CD4⁺ 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 CD4⁺ naïve T cells via production of CCL17 and CCL22.

These data suggest that CCL17 and CCL22 produced by TSLP-primed naïve CD4⁺ T cells in asthma might contribute to an increase in Th2 cells via autocrine loops.