title: Adjuvant properties of thermal component of hyperthermia enhanced transdermal immunization: effect on dendritic cells.
abstract: Hyperthermia enhanced transdermal (HET) immunization is a novel needle free immunization strategy employing application of antigen along with mild local hyperthermia (42°C) to intact skin resulting in detectable antigen specific Ig in serum. In the present study, we investigated the adjuvant effect of thermal component of HET immunization in terms of maturation of dendritic cells and its implication on the quality of the immune outcome in terms of antibody production upon HET immunization with tetanus toxoid (TT). We have shown that in vitro hyperthermia exposure at 42°C for 30 minutes up regulates the surface expression of maturation markers on bone marrow derived DCs. This observation correlated in vivo with an increased and accelerated expression of maturation markers on DCs in the draining lymph node upon HET immunization in mice. This effect was found to be independent of the antigen delivered and depends only on the thermal component of HET immunization. In vitro hyperthermia also led to enhanced capacity to stimulate CD4+ T cells in allo MLR and promotes the secretion of IL-10 by BMDCs, suggesting a potential for Th2 skewing of T cell response. HET immunization also induced a systemic T cell response to TT, as suggested by proliferation of splenocytes from immunized animal upon in vitro stimulation by TT. Exposure to heat during primary immunization led to generation of mainly IgG class of antibodies upon boosting, similar to the use of conventional alum adjuvant, thus highlighting the adjuvant potential of heat during HET immunization. Lastly, we have shown that mice immunized by tetanus toxoid using HET route exhibited protection against challenge with a lethal dose of tetanus toxin. Thus, in addition to being a painless, needle free delivery system it also has an immune modulatory potential.
authors.affiliation: National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Joshi
authors.forename: Vikas
authors.initials: V
authors.lastname: Duhan
authors.forename: Neelam
authors.initials: N
authors.lastname: Lingwal
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Bhaskar
authors.forename: Pramod
authors.initials: P
authors.lastname: Upadhyay
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000279:Administration, Cutaneous; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects; D000071858:Epithelial Cell Adhesion Molecule; D005452:Fluoresceins / Q000378:metabolism; D006979:Hyperthermia, Induced; D007114:Immunization; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000187:drug effects; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D009339:Needles; D009500:Neutralization Tests; D013388:Succinimides / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013745:Tetanus Toxoid / Q000633:toxicity; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016207:Cytokines; D000071858:Epithelial Cell Adhesion Molecule; D005452:Fluoresceins; D013388:Succinimides; D013745:Tetanus Toxoid