K+Channels As A Potential Target For Immunomodulation Of CD4+CD28Null T Cells In Patients With Acute Coronary Syndrome

Objective To investigate the surface phenotype and K+channel expression of CD4+CD28nu11T cells from patients with acute coronary syndrome (ACS). Methods CD4+CD28nu11T cells were isolated from peripheral blood of ACS patients and healthy controls by using MACS beads. Surface phenotype was analyzed by flow cytometry, while Channel expression was studied before or after stimulation in the whole-cell mode of the patch-clamp technique. Real time-PCR was used to test the effect of Kv1.3and KCa3.1blocker on the production of inflammatory factors of CD4+CD28nu11T cells. Results We found that more than80%of CD4+CD28nu11T cells in patients with ACS showed a CD45RA"CD45RO+CCR7-surface phenotype. CD4+CD28nu11T cells expressed small numbers of the voltage-gated Kvl.3and intermediate-conductance Ca2+-activated K+channel KCa3.1when quiescent, but increased Kvl.3expression4-fold with little change in KCa3.1levels upon activation. Consistent with their channel phenotypes, the production of interferon-y and perforin in CD4+CD28nu11T cells was suppressed by the specific Kv1.3blocker PAP-1. Conclusions Therefore, selective targeting of Kv1.3in CD4+CD28nu11T cells may hold potential therapeutic promise for ACS.