Mucosal anti-CD3 monoclonal antibody attenuates collagen-induced arthritis that is associated with induction of LAP+ regulatory T cells and is enhanced by administration of an emulsome-based Th2-skewing adjuvant.

Abstract

Mucosal (nasal or oral) administration of anti-CD3 mAb is effective in ameliorating animal models of autoimmunity (experimental autoimmune encephalomyelitis, diabetes, and lupus) by inducing LAP(+) regulatory T cells. We tested this approach in an arthritis model using type II collagen. We found that nasal anti-CD3 was more effective than oral anti-CD3 in attenuating the development of arthritis. Nasal anti-CD3 induced a LAP(+) regulatory T cell that secreted high levels of IL-10 and suppressed collagen-specific T cell proliferation and anti-collagen Ab production. However, neither nasal nor oral anti-CD3 attenuated disease when given to animals with ongoing arthritis, and this was associated with a lack of induction of LAP(+) regulatory T cells. We found, however, that coadministration of a novel emulsome adjuvant, which enhances Th2 responses, resulted in the induction of LAP(+) regulatory T cells and suppression of ongoing arthritis by both nasal and oral anti-CD3. Suppression of arthritis by mucosal anti-CD3 was associated with less joint damage, a decrease of TNF-alpha and IFN-gamma mRNA expression in joints, and a reduction in anti-collagen Abs. These results demonstrate that mucosal anti-CD3 therapy may serve as a therapeutic approach in arthritis and that the biologic effect is enhanced by an emulsome-based adjuvant.

• Authors: Henry Yim Wu, Ruth Maron, Ann-Marcia Tukpah, Howard L Weiner
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 185 Issue 6 Pg. 3401-7 (Sep 15 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20720210 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Adjuvants, Immunologic
• Antibodies, Monoclonal
• CD3 Complex
• Collagen Type II
• Emulsions
• Peptides
• Protein Precursors
• Transforming Growth Factor beta
• latency-associated propeptide, TGF-beta

Topics

• Adjuvants, Immunologic (administration & dosage, pharmacology)
• Animals
• Antibodies, Monoclonal (administration & dosage, physiology)
• Arthritis, Experimental (immunology, pathology, prevention & control)
• CD3 Complex (immunology)
• Cell Differentiation (immunology)
• Cells, Cultured
• Collagen Type II (toxicity)
• Emulsions
• Male
• Mice
• Mice, Inbred DBA
• Mouth Mucosa (immunology, metabolism)
• Nasal Mucosa (immunology, metabolism)
• Peptides (physiology)
• Protein Precursors (biosynthesis, physiology)
• T-Lymphocytes, Regulatory (immunology, metabolism, pathology)
• Th2 Cells (immunology, pathology)
• Transforming Growth Factor beta (biosynthesis, physiology)
• Up-Regulation (immunology)