Immune active effects of chemokine RANTES on human peripheral mononuclear cells

Abstract

Objective To investigate the proliferation and phenotypes of peripheral mononuclear cells (PMNC) stimulated by recombinant human RANTES (rhRANTES) and the mechanisms involved.Methods PMNC was stimulated by various concentrations of rhRANTES and/or anti-CD3 mAb and intervened by PDTC and CTLA4Ig. Scintillation counter was used to count the cpm of proliferation cells and flow cytometry was used to detect the phenotypes of lymphocytes.Results rhRANTES was capable of directly stimulating purified human PMNC proliferation and two peaks occurred with rhRANTES concentration of 100 ng/ml and 5000 ng/ml respectively. The proliferation of PMNC stimulated by rhRNATES was significantly higher than that in the presence of anti-CD3mAb (P 0.05). The immune active effects of rhRANTES could be inhibited by PDTC or CTLA4Ig in a dose dependent manner. RANTES treatment of PMNC in vitro increased the level of cell surface CD25 and decreased the CCR5 expression. But it did not influence the ratio of CD4/CD8 and CD28 expression of lymphocytes.Conclusion RANTES is an important stimulatory mediator in human PMNC activation. This special signal works depending on the activation of IL-2 signal pathway, CD28 costimulatory pathway and nuclear factor-κB, but independent of CD3 activation.