title: CTLA-4-Tg/CD-28-KO Mice Exhibit Reduced T Cell Proliferation in vivo Compared to CD-28-KO Mice in a Graft-versus-host Disease Model.
abstract: Activated T cells express inhibitory receptors such as CTLA-4 that can downregulate immune responses. Blockade of or genetic deficiency in CTLA-4 can result in autoimmunity. Therefore, strategies to increase the inhibitory function of CTLA-4 may be attractive in settings of undesirable T cell responses such as autoimmunity or transplant rejection. We have tested the hypothesis that transgenic constitutive expression of CTLA-4 can further attenuate immune responses when compared with normal inducible expression. Our results indicate that transgenic expression of CTLA-4 in mouse T cells (CTLA-4-Tg T cells) results in reduced cell cycle progression and increased apoptosis of TCR-stimulated T cells. CTLA-4-Tg T cells display reduced T cell proliferation in an in vivo model of graft versus host disease (GVHD). These results further our understanding of how CTLA-4 can be manipulated to inhibit immune responses and may help development of new therapeutic strategies for clinical settings of autoimmunity and transplantation.
authors.affiliation: Laboratory of Host Defense Modulation, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea.
authors.forename: Jong-Sun
authors.initials: JS
authors.lastname: Yoo
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Lee
authors.forename: Joo Won
authors.initials: JW
authors.lastname: Yoon
authors.forename: Kyeong Eun
authors.initials: KE
authors.lastname: Hyung
authors.forename: Kwang Woo
authors.initials: KW
authors.lastname: Hwang
keywords: Cell surface molecules; Cellular activation; Rodent; T lymphocytes; Transgenic