Combination of Nasal Lymphotactin and Macrophage Chemoattractant Protein-1 Expressing Plasmids Elicits Antigen-Specific Salivary S-IgA Antibody Immunity

Abstract

It has been shown that mucosal application of chemokines with protein antigen (Ag) successfully induces mucosal and systemic antibody (Ab) responses, as well as CD4+ T cell responses. We examined whether plasmids expressing lymphotaction (LTN) and/or macrophage chemoattractant proteine-1 (MCP-1) cDNA (pLTN and pMCP-1) exhibit nasal adjuvanticity when administered with protein Ag. When either pLTN or pMCP-1 was employed as a nasal adjuvant in mice, OVA-specific IgG Ab responses were seen in plasma ; however, both failed to induce OVA-specific secretory IgA (S-IgA) Abs in external secretions except anti-OVA IgG and IgA Abs in nasal washes of mice given pLTN. However, mice nasally immunized with a combination of pLTN and pMCP-1 showed OVA-specific S-IgA Ab responses in both saliva and fecal extracts. Further, that combination of chemokines used as a nasal adjuvant induced the highest levels of CD4+ T cell proliferative and Th2-type cytokine responses in cervical lymph nodes (CLN), as compared with a single chemokine nasal administration. In addition, a significantly increased number of CD11c+ dendritic cells (DCs) which expressed co-stimulatory molecules such as MHC II, CD40 and CD86 noted in the nasopharyngeal-associated lymphoreticular tissue (NALT) of mice given pLTN and pMCP-1. These results show that a combination of pLTN and pMCP-1 given as a nasal adjuvant induces optimal mucosal S-IgA Ab responses in submandibular glands, which are mediated by increased number of DCs in the NALT and Th2-type CD4+ T cells in the CLN.