Epicutaneous Immunization with TNP-Ig and Zymosan Induces TCRαβ+ CD4+ Contrasuppressor Cells That Reverse Skin-Induced Suppression via IL-17A

Abstract

Background: Our previous work showed that epicutaneous (EC) immunization with protein antigen e.g. TNP-conjugated mouse immunoglobulin (TNP-Ig) in the form of a patch prior to hapten sensitization inhibits Th1-mediated contact hypersensitivity (CHS) in mice. We also found that suppression of CHS was mediated by TCRαβ+ CD4+ CD8+ T suppressor cells producing TGF-β. The aim of this study was to investigate the role of innate immunity in the suppression of CHS. Methods: Mice were immunized by applying gauze patches containing protein antigen alone or in the presence of zymosan, and were then tested for the CHS response. Adoptive cell transfer experiments were used to study the mechanisms involved in the reversal of skin-induced suppression. The influence of EC immunization on cytokine production by lymph node cells was measured by ELISA. Results: We found that EC immunization with TNP-Ig and zymosan before trinitrophenyl chloride sensitization reverses skin-induced suppression, demonstrated in vivo and in vitro. The reversal of skin-induced suppression was transferable by antigen-specific TCRαβ+ CD4+ T contrasuppressor cells. Furthermore, we showed that the contrasuppression was IL-17A-dependent and TLR2- and MyD88-independent. Conclusions: Our work strongly suggests that EC immunization with protein antigen and zymosan reverses skin-induced suppression and that this approach may be a potential tool to increase the immunogenicity of weakly immunogenic antigens.

Diet‐induced obesity aggravates NK cell–mediated contact hypersensitivity reaction in Rag1−/− mice

“…To assess vascular permeability, 21 sensitized or naive mice were challenged with 5 μL 0.2% DNFB and then injected with 1% Evans Blue (EB)dye (83 μg/g body weight) 23 hours later. After 1 hour, mice were sacrificed and ø 6‐mm punches of the ears were collected.…”

Regulation of contact sensitivity in non‐obese diabetic (NOD) mice by innate immunity

“…Cutaneous delayed‐type hypersensitivity and related contact hypersensitivity (CHS) reactions are classic examples of antigen‐specific T cell‐mediated allergic immune responses in the skin . CHS responses can be initiated by keratinocytes and dendritic cells (DCs) .…”

Obesity aggravates contact hypersensitivity reaction in mice

“…CHS can be transferred into naive syngeneic recipients by intravenous injection of T effector cells 25 . To determine if the exacerbated CHS seen in HFDIO mice is transferable, we performed adoptive cell‐transfer experiments.…”

“…CHS can be transferred into naive syngeneic recipients by intravenous injection of T effector cells. 25 To determine if the exacerbated CHS seen in HFDIO mice is transferable, we performed adoptive celltransfer experiments. Naive recipient mice were challenged with TNCB after receiving axillary and inguinal lymph node cells (ALNCs) or splenocytes (SPLCs) from TNCB-sensitized ND-fed lean donors or TNCB-sensitized HFD-fed obese donors.…”