Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein transduction domain prevents allergic inflammation

Je-Min Choi ¹, Mi-Hyun Ahn , Wook-Jin Chae , Yung-Gook Jung , Jae-Chul Park , Hyun-Mi Song , Young-Eun Kim , Jung-Ah Shin , Choon-Sik Park , Jung-Won Park , Tae-Kwann Park , Jung-Hoon Lee , Byung-Fhy Seo , Kyun-Do Kim , Eun-Sung Kim , Dong-Ho Lee , Seung-Kyou Lee , Sang-Kyou Lee

Affiliations

¹ Department of Biotechnology, College of Engineering, Yonsei University, Seoul 120-749, Republic of Korea.

PMID: 16604087
56 citations

Abstract

CTLA-4 is a negative regulator of T-cell activation, and its inhibitory effects can be accomplished either by competition with CD28 or by transmitting negative signals through its intracellular domain. To utilize the cytoplasmic domain of CTLA-4 to suppress allergic inflammation, we fused it to a novel protein-transduction domain in the human transcriptional factor Hph-1. Transduction efficiency was verified in vitro and in vivo after ocular, intranasal and intradermal administration. After transduction into T cells, the Hph-1-ctCTLA-4 fusion protein inhibited the production of interleukin (IL)-2, and downregulated CD69 and CD25. Intranasal administration of Hph-1-ctCTLA-4 resulted in markedly reduced infiltration of inflammatory cells, secretion of T helper type 2 (T(H)2) cytokines, serum IgE levels and airway hyper-responsiveness in a mouse model of allergic airway inflammation. These results indicated that Hph-1-ctCTLA-4 constitutes an effective immunosuppressive protein drug for potential use in the treatment of allergic asthma, via nasal administration.

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