Marked enhancement of antigen‐specific T‐cell responses by IL‐7‐fused nonlytic, but not lytic, Fc as a genetic adjuvant

HJ Nam, MY Song, DH Choi, SH Yang… - European journal of …, 2010 - Wiley Online Library
HJ Nam, MY Song, DH Choi, SH Yang, HT Jin, YC Sung
European journal of immunology, 2010Wiley Online Library
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‐Fcm) 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 …
Abstract
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‐Fcm) 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.
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