This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Isobe, M. Articles by Sekiguchi, M. Search for Related Content PubMed PubMed Citation Articles by Isobe, M. Articles by Sekiguchi, M.

(Circulation. 1997;96:2247-2253.)
© 1997 American Heart Association, Inc.

Articles

Regulation by Differential Development of Th1 and Th2 Cells in Peripheral Tolerance to Cardiac Allograft Induced by Blocking ICAM-1/LFA-1 Adhesion

Mitsuaki Isobe, MD; Jun-ichi Suzuki, MD; Satoshi Yamazaki, MD; Yoshikazu Yazaki, MD; Shiro Horie, MD; Yoshio Okubo, MD; Koji Maemura, MD; Yoshio Yazaki, MD; ; Morie Sekiguchi, MD

From the First Department of Internal Medicine, Shinshu University School of Medicine (M.I., J.S., S.Y., Yoshikazu Yazaki, S.H., Y.O., M.S.), and The Third Department of Internal Medicine, University of Tokyo (K.M., Yoshio Yazaki), Japan.

Correspondence to Mitsuaki Isobe, MD, The First Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390 Japan. E-mail isobemi{at}gipac.shinshu-u.ac.jp

Background Specific immune tolerance to cardiac allografts is induced by anti–ICAM-1 and anti–LFA-1 MAbs. Although the expression of the Th1 cytokines IL-2 and IFN- is shown to increase in association with acute rejection, the roles of cytokines in the induction of peripheral tolerance by anti–ICAM-1 and anti–LFA-1 MAbs are not yet known.

Methods and Results BALB/c hearts were transplanted into C3H/He mice. The MAbs to ICAM-1 and LFA-1 were injected for 3 days after transplantation in some recipients, and others were treated with FK506. IL-2 concentration in the supernatant of splenocytes from MAb-treated mice that were mix-cultured with donor splenocytes was lower than in normal controls. The expression of Th1 cytokines, detected by Northern blot assay, was enhanced in grafts or spleens of nontreated mice, whereas Th2 cytokines were expressed in the spleens of MAb-treated mice. No cytokine expression was enhanced in mice treated with FK506. Also, the induction of tolerance was prevented by the administration of rIL-2 in vivo in 5 of 7 mice, which were rendered tolerant.

Conclusions These data provide evidence that impairment of IL-2 production is critically involved in this tolerance induction and suggest that predominance of Th2 over Th1 cells is essential for tolerance induction by antiadhesion therapy.

Key Words: cytokines • interleukins • glycoproteins • immunology • transplantation • immune system • rejection

This article has been cited by other articles:

				M. Isobe, H. Kosuge, and J.-i. Suzuki T Cell Costimulation in the Development of Cardiac Allograft Vasculopathy: Potential Targets for Therapeutic Interventions Arterioscler Thromb Vasc Biol, July 1, 2006; 26(7): 1447 - 1456. [Abstract] [Full Text] [PDF]

				Q.-W. Zhang, D. D. Kish, and R. L. Fairchild Absence of Allograft ICAM-1 Attenuates Alloantigen-Specific T Cell Priming, But Not Primed T Cell Trafficking into the Graft, to Mediate Acute Rejection J. Immunol., June 1, 2003; 170(11): 5530 - 5537. [Abstract] [Full Text] [PDF]

				A. D. Straw, A. S. MacDonald, E. Y. Denkers, and E. J. Pearce CD154 Plays a Central Role in Regulating Dendritic Cell Activation During Infections That Induce Th1 or Th2 Responses J. Immunol., January 15, 2003; 170(2): 727 - 734. [Abstract] [Full Text] [PDF]

				H. H. Smits, E. C. de Jong, J. H. N. Schuitemaker, T. B. H. Geijtenbeek, Y. van Kooyk, M. L. Kapsenberg, and E. A. Wierenga Intercellular Adhesion Molecule-1/LFA-1 Ligation Favors Human Th1 Development J. Immunol., February 15, 2002; 168(4): 1710 - 1716. [Abstract] [Full Text] [PDF]

				D. Bechard, A. Scherpereel, H. Hammad, T. Gentina, A. Tsicopoulos, M. Aumercier, J. Pestel, J.-P. Dessaint, A.-B. Tonnel, and P. Lassalle Human Endothelial-Cell Specific Molecule-1 Binds Directly to the Integrin CD11a/CD18 (LFA-1) and Blocks Binding to Intercellular Adhesion Molecule-1 J. Immunol., September 15, 2001; 167(6): 3099 - 3106. [Abstract] [Full Text] [PDF]

				B. M. Spriewald, M. Hara, A. Bushell, S. Jenkins, P. J. Morris, and K. J. Wood Differential Role for Competitive Reverse Transcriptase-Polymerase Chain Reaction and Intracellular Cytokine Staining as Diagnostic Tools for the Assessment of Intragraft Cytokine Profiles in Rejecting and Nonrejecting Heart Allografts Am. J. Pathol., November 1, 2000; 157(5): 1453 - 1458. [Abstract] [Full Text] [PDF]

				J.-i. Suzuki, M. Isobe, S. Yamazaki, S. Horie, Y. Okubo, and M. Sekiguchi Sensitive diagnosis of cardiac allograft rejection by detection of cytokine transcription in situ Cardiovasc Res, November 1, 1998; 40(2): 307 - 313. [Abstract] [Full Text] [PDF]

				K.-i. Seino, K. Fukao, K. Muramoto, K. Yanagisawa, Y. Takada, S. Kakuta, Y. Iwakura, L. Van Kaer, K. Takeda, T. Nakayama, et al. Requirement for natural killer T (NKT) cells in the induction of allograft tolerance PNAS, February 27, 2001; 98(5): 2577 - 2581. [Abstract] [Full Text] [PDF]