Adjuvant selection regulates gut migration and phenotypic diversity of antigen-specific CD4
| Autor: | D R, Frederick, J A, Goggins, L M, Sabbagh, L C, Freytag, J D, Clements, J B, McLachlan |
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| Rok vydání: | 2016 |
| Předmět: |
CD4-Positive T-Lymphocytes
Diarrhea Integrin beta Chains Integrin alpha4 Receptors Lymphocyte Homing chemical and pharmacologic phenomena Dendritic cells Article Enterotoxins Mice Adjuvants Immunologic Mucosal immunity Cell Movement Animals Enterotoxigenic Escherichia coli Humans Infusions Parenteral Immunity Mucosal Cells Cultured Escherichia coli Infections Adjuvant Vaccines Escherichia coli Vaccines Escherichia coli Proteins CD4+ T cells Intestines Phenotype Mutation Immunization |
| Zdroj: | Mucosal immunology |
| ISSN: | 1935-3456 |
| Popis: | Infectious diarrheal diseases are the second leading cause of death in children under five, making vaccines against these diseases a high priority. It is known that certain vaccine adjuvants, chiefly bacterial ADP-ribosylating enterotoxins, can induce mucosal antibodies when delivered parenterally. Based on this, we reasoned vaccine-specific mucosal cellular immunity could be induced via parenteral immunization with these adjuvants. Here, we show that, in contrast to the TLR9 agonist CpG, intradermal immunization with non-toxic double-mutant heat-labile toxin from enterotoxigenic E. coli drives endogenous, antigen-specific CD4+ T cells to expand and upregulate the gut-homing integrin α4β7. This was followed by T cell migration into gut-draining lymph nodes and both small and large intestines. We also find dmLT produces a balanced Th1 and Th17 response whereas T cells from CpG immunized mice are predominantly Th1. Immunization with dmLT preferentially engages CD103+ dendritic cells compared to CpG, and mice deficient in CD103+ dendritic cells were unable to fully license antigen-specific T cell migration to the mucosae following parenteral immunization. This work has the potential to redirect the design of existing and next generation vaccines to elicit pathogen-specific immunity in the intestinal tract with non-mucosal immunization. |
| Databáze: | OpenAIRE |
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