Differential expression of Th2 chemokine receptors on T cells from atopic and nonatopic asthmatics in response to Der p 1-pulsed dendritic cells

Abstract

Background: In vitro polarized human Th2 cells preferentially express the chemokine receptors CCR3 and CCR4 and migrate to their ligands: eotaxin, monocyte-derived chemokine (MDC) or CCL22, thymus- and activation-regulated chemokine (TARC) or CCL17. However, little is known about the regulation of these chemokine receptor axes by Der p 1-pulsed dendritic cells in house dust mite (HDM)-sensitive and non-atopic asthmatics. Objective: The aim was to investigate the modulatory effects of Der p 1-pulsed DCs on the expression of CCR3 and CCR4 on CD4+ T cells of HDM-sensitive and non-atopic asthmatics. Material and Method: Using real-time RT-PCR and flow cytometry analysis, the expression of CCR3 and CCR4 were assessed in autologous CD4+ T cells after co-incubation with Der p 1-pulsed DCs from these two asthmatic groups. We also determined the mRNA expression of CCR4 ligands TARC/CCL17 and MDC/CCL22 in monocyte-derived DCs after Der p 1 pulsation. Results: We performed flow cytometry analysis of CD4+ T cells from HDM-sensitive and non-atopic asthmatics, taken 24 and 48 h after co-incubation with Der p 1-pulsed DCs. We demonstrated that after co-incubation, there was a significant increase in CCR3+ and CCR4+ CD4+ T cells from HDM-sensitive asthmatics, which began to occur at 24 h and 48 h respectively, and corresponded to their expression at mRNA levels. In contrast, only CCR4 mRNA but not protein expression was increased in non-atopic CD4+ T cells. After Der p 1 pulsation, mRNA expression of CCR4-specific ligands (CCL17 and CCL22) was also markedly upregulated in HDM-sensitive DCs whereas only CCL17 gene expression was increased in non-atopic DCs. Conclusion: These data support the role of DCs in differential regulation of CCR3 and CCR4 on CD4+ T cells from HDM-sensitive and non-atopic asthmatics after Der p 1 exposure.