Epicutaneous (EC) immunization with type II collagen (COLL II) induces CD4(+) CD8(+) T suppressor cells that protect from collagen-induced arthritis (CIA)

Abstract

Background: We have shown previously that epicutaneous (EC) immunization with protein antigen induces T suppressor cells that alleviate inflammatory response in contact hypersensitivity reactions, in an animal model of multiple sclerosis, and in TNBS-induced colitis.

Methods: DBA/1 mice were EC immunized with type II collagen (COLL II) spread over a gauze patch on days 0 and 4. On day 7, patches were removed and mice were intradermally (id) immunized with COLL II in CFA to induce collagen-induced arthritis (CIA).

Results: Our work shows that EC immunization with 100μg of COLL II prior to CIA induction reduces disease severity as determined by macroscopic evaluation. Reduced disease severity after EC immunization with COLL II correlates with milder histological changes found in joint sections. Experiments with the three non-cross-reacting antigens COLL II, ovalbumin (OVA) and myelin basic protein (MBP) showed that skin-induced suppression is antigen non-specific. Transfer experiments show that EC immunization with COLL II induces suppressor cells that belong to the population of CD4(+) CD8(+) double positive lymphocytes. Flow cytometry experiments showed increased percentage of CD4(+) CD8(+) RORγt(+) cells in axillary and inguinal lymph nodes isolated from mice patched with COLL II.

Conclusion: Maneuver of EC immunization with a protein antigen that induces suppressor cells to inhibit inflammatory responses may become an attractive, noninvasive, needle-free therapeutic method for different clinical situations.

Keywords: CD4(+)CD8(+)RORγt(+) suppressor T cells; Collagen-induced arthritis; Cytokines; Epicutaneous immunization.