Marked enhancement of antigen-specific T-cell responses by IL-7-fused nonlytic, but not lytic, Fc as a genetic adjuvant.
IL-7 plays a crucial role in the homeostatic proliferation, differentiation and survival of T cells, as well as in the survival and proliferation of precursor B cells. Here, we demonstrated that utilizing nonlytic Fc-fused IL-7 (IL-7-Fc(m)) as a genetic adjuvant significantly enhanced not only CD4(+) but also CD8(+) T-cell responses by E7 DNA immunization, in addition to improving protection against TC-1-induced tumors in comparison to IL-7 alone. Similar results were obtained in OT-1 adoptive transfer experiments with OVA DNA injection, suggesting independence from antigenic nature and experimental conditions. In particular, the increased frequency of CD8(+) T cells was mainly due to enhanced T-cell proliferation in T-cell priming, and not to decreased cellular apoptosis. Interestingly, the enhanced adjuvant effect was not seen in the co-delivery of lytic Fc-fused IL-7 (IL-7-Fc) which increases T-cell apoptosis as well as T-cell proliferation, suggesting that the T-cell proliferative effect may be neutralized by T-cell apoptosis. Thus, our findings suggest that nonlytic Fc, in contrast to lytic Fc, fusion to cytokines may provide an insight in designing a potent genetic adjuvant for inducing CD4(+) and CD8(+) T-cell responses.
Nam
Hyo Jung
HJ
Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea.
Song
Mi-Young
MY
Choi
Dong-Hoon
DH
Yang
Se-Hwan
SH
Jin
Hyun-Tak
HT
Sung
Young-Chul
YC
D000276:Adjuvants, Immunologic; D000818:Animals; D000941:Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016219:Immunotherapy, Adoptive; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000276:immunology
D000276:Adjuvants, Immunologic; D000941:Antigens; D007141:Immunoglobulin Fc Fragments; D015851:Interleukin-7; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16; D010047:Ovalbumin