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-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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic
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Animals
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Antigens / immunology*
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cell Line, Tumor
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Female
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Flow Cytometry
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Humans
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Immunoglobulin Fc Fragments / genetics
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Immunoglobulin Fc Fragments / immunology*
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Immunoglobulin Fc Fragments / metabolism
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Immunotherapy, Adoptive
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Interleukin-7 / genetics
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Interleukin-7 / immunology*
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Interleukin-7 / metabolism
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Mice
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Mice, Inbred C57BL
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Neoplasms, Experimental / immunology
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Neoplasms, Experimental / pathology
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Neoplasms, Experimental / therapy
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Oncogene Proteins, Viral / genetics
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Oncogene Proteins, Viral / immunology
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Oncogene Proteins, Viral / metabolism
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Ovalbumin / immunology
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Papillomavirus E7 Proteins
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Vaccination / methods
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Vaccines, DNA / immunology
Substances
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Adjuvants, Immunologic
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Antigens
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Immunoglobulin Fc Fragments
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Interleukin-7
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Oncogene Proteins, Viral
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Papillomavirus E7 Proteins
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Vaccines, DNA
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oncogene protein E7, Human papillomavirus type 16
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Ovalbumin