Enhancement of antigen-specific CD8 T cell responses by co-delivery of Fc-fused CXCL11.
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-γ and TNF-α) 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.
Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
Hong
H
Namkoong
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
Mi-Young
MY
Song
Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
Yong Bok
YB
Seo
Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
Dong-Hoon
DH
Choi
Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
Sae Won
SW
Kim
Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
Se Jin
SJ
Im
Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea. Electronic address: ycsung@postech.ac.kr.
Young Chul
YC
Sung
Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea. Electronic address: yunji@postech.ac.kr.
Yunji
Y
Park
D000256:Adenoviridae; D000276:Adjuvants, Immunologic / Q000235:genetics*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology; D054371:Chemokine CXCL11 / Q000235:genetics / Q000276:immunology*; D054370:Chemokine CXCL9 / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005260:Female; D057809:HEK293 Cells; D052162:Human papillomavirus 16; D006801:Humans; D007111:Immunity, Cellular; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000628:therapy; D050725:Papillomavirus E7 Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; C485433:Cxcl10 protein, mouse; C515203:Cxcl11 protein, mouse; C485969:Cxcl9 protein, mouse; D016207:Cytokines; D007141:Immunoglobulin Fc Fragments; D050725:Papillomavirus E7 Proteins
Adjuvant; CD8 T cell; CXCL11; Memory; Vaccination