Enhancement of antigen-specific CD8 T cell responses by co-delivery of Fc-fused CXCL11

Abstract

Chemokines have been known to play an important role in eliciting adaptive immune responses by, selectively attracting the innate cellular components to the site of antigen presentation. In this study, we demonstrated that all three CXCR3 ligands, CXCL9, CXCL10, and CXCL11, could act as a strong, genetic adjuvant. Among them, CXCL11 increased vaccine antigen-specific CD8 T cells, including, several cytokine secretions (IFN-gamma and TNF-alpha) to a greater degree than the other two CXCR3 ligands. Fc-fusion of CXCL11 (CXCL11-Fc) induced similar but slightly higher CD8 T cell response, which, appeared to be antigen(ovalbumin (OVA) vs. human papillomavirus 16 (HPV16) E7) and vaccine, type- (adenovirus vs. DNA vaccine) independent. In addition, the adjuvant effect of CXCL11-Fc was, further confirmed by suppressing tumor growth and extension of survival rates in a therapeutic tumor, model, which was correlated with enhanced antigen-specific CD8 T cell responses. Interestingly, the, enhanced antigen-specific CD8 T cell responses by co-delivery of CXCL11-Fc were associated with CD8, T cell proliferation, followed by increased total and effector memory T cell frequencies. Taken together, our findings provide a novel role of CXCL11 as a strong genetic adjuvant which might be used to, increase antigen-specific CD8 T cell immunity elicited by vaccination. (C) 2013 Elsevier Ltd. All rights reserved.