002 - The chemokine CCL18 turns memory CD4⁺ T cells from non-allergic subjects into T cells expressing a regulatory phenotype - 05/12/08

Introduction: CCL18 (Pulmonary and Activation-Regulated Chemokine, PARC) is expressed at high level in human’s lung and induced by Th2 cytokines. In the laboratory we have shown that CCL18 is increased in allergic asthma, however its role remains unclear. Beside their chemoattractant role, chemokines can also directly activate T cells. In this study, we investigated the effect of CCL18 on memory CD4⁺ T cells.

Methods: CD4⁺CD45RO⁺ memory T cells were isolated from PBMC of non-allergic subjects and treated with human recombinant CCL18 for 2 h 30. Cells were then stimulated by anti-CD3 mAb and anti-CD28 mAb to evaluate the cytokine profile by ELISA. The phenotypes related to regulatory T cells were evaluated by flow cytometry. The suppressive effect of CCL18-treated memory T cells was examined by incorporation of H3-thymidine in cocultures with CD4⁺CD25^– effector T cells. Real-time PCR was performed to assess Foxp3 mRNA expression.

Results: CCL18-treated memory T cells exhibited an increased production of IL-10 and TGF-β1 compared with controls. The extracellular expression of CD103, CTLA-4 and TGF-β1 as well as the intracellular expression of Foxp3 were elevated by in CCL18- treated memory cells. Moreover, these cells inhibited the proliferation of CD4⁺CD25^– effector T cells. The expression of Foxp3 at the transcriptional level correlated with that of the protein.

Conclusion: This study suggests that short-time CCL18 treatment may switch memory CD4⁺ T cells into regulatory T cells in non-allergic subjects, which may play a role in the homeostasis of regulatory T cells in the periphery and may participate to the suppression of immune responses to allergens in non-allergic subjects.