Generation and evaluation of the efficacy of rhesus monkey soluble cytotoxic T lymphocyte-associated antigen-4 in the al
- PDF / 373,717 Bytes
- 7 Pages / 547.087 x 737.008 pts Page_size
- 68 Downloads / 175 Views
ORIGINAL RESEARCH PAPER
Generation and evaluation of the efficacy of rhesus monkey soluble cytotoxic T lymphocyte-associated antigen-4 in the allogeneic mixed lymphocyte reaction Jung-Sik Kim • Inho Choi • Han-Hyoung Lee • Suk Jun Lee • Manheum Na • Sang-Hoon Kim • Jihye Han • Joonbeom Bae • Sang-Pil Choi • Sang Joon Kim Chung-Gyu Park • Taehoon Chun
•
Received: 17 May 2012 / Accepted: 14 August 2012 / Published online: 31 August 2012 Ó Springer Science+Business Media B.V. 2012
Abstract Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4; CD152) is a transmembrane protein that is structurally similar to CD28. As CTLA-4 has a much higher binding affinity to B7 than CD28, several approaches using soluble CTLA-4 have been tried to down-regulate T cell activity by blocking the interaction between CD28 and B7. We constructed soluble
Jung-Sik Kim and Inho Choi are contributed equally to this study. J.-S. Kim C.-G. Park Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea J.-S. Kim S. J. Kim C.-G. Park Xenotransplantation Research Center, Seoul National University Hospital, Seoul 110-799, Republic of Korea I. Choi School of Biotechnology, Yeungnam University, Gyeongsan 712-749, Republic of Korea H.-H. Lee S. J. Lee M. Na S.-H. Kim J. Han J. Bae S.-P. Choi T. Chun (&) Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea e-mail: [email protected] S. J. Kim Department of Surgery, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea
rhesus monkey CTLA-4 immunoglobulin (CTLA4Ig) containing a critical binding site to B7 combined with a constant Ig heavy chain region in a mammalian system. Flow cytometry analyses indicated that soluble rhesus monkey CTLA-4Ig bound to rhesus monkey CD86 (B7.2). Moreover, soluble rhesus monkey CTLA-4Ig more effectively blocked the rhesus monkey–rhesus monkey allogeneic mixed lymphocyte reaction compared with that of humans. These results indicate that soluble rhesus monkey CTLA-4Ig may be useful in preclinical trials in a rhesus monkey model. Keywords Allogeneic response Co-stimulatory molecule Cytotoxic T lymphocyte-associated antigen-4 Mixed lymphocyte reaction Rhesus monkey T cells
Introduction Cytotoxic T lymphocyte-associated antigen-4 (CTLA4; CD152) was originally identified on the surface of activated cytotoxic T cells (CD8? T cells) (Brunet et al. 1987). Further study revealed that CTLA-4 is highly inducible on the surface of all types of activated T cells (Chambers et al. 2001). Based on biochemical analyses, CTLA-4 is a structural homolog of CD28, and both proteins bind to B7 molecules (B7.1 and B7.2; CD80 and CD86) expressed on professional antigen
123
2192
presenting cells (Chambers et al. 2001). Therefore, the functional role of CD28 or CTLA-4 has been proposed to be important for the interaction between T cells and professional antigen presenting cells. However, the role of CTLA-4 o
Data Loading...
