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

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• 作者：Katarzyna Marcińska^a ; Monika Majewska-Szczepanik^a ; Agata Lazar^b ; Paulina Kowalczyk^a ; Dominika Biała^a ; Dorota Woźniak^a ; Marian Szczepanik^a ; ^{mmszczep@cyf-kr.edu.pl" class="auth_mail" title="E-mail the corresponding author} ; ^{marian.szczepanik@uj.edu.pl" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Ab ; antibody ; ALNC ; axillary and inguinal lymph node cells ; anti-CPP ; Anti-cyclic citrullinated peptide ; CFA ; complete Freund's adjuvants ; CHS ; contact hypersensitivity reactions ; CIA ; collagen-induced arthritis ; COLL II ; type II collagen ; EAE ; experimental autoimmune encephalomyelitis ; EC ; epicutaneous ; FBS ; fetal bovine serum ; id ; intradermally ; IFA ; incomplete Freund's adjuvants ; Ig ; immunoglobulin ; IL ; interleukin ; ip ; intraperitoneally ; iv ; intravenous ; LPS ; lipopolysaccharide ; MBP ; myelin
• 刊名：Pharmacological Reports
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：68
• 期：2
• 页码：483-489
• 全文大小：1710 K

文摘

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 100 μg 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.