Superagonist CD28 Antibody Preferentially Expanded Foxp3-Expressing nTreg Cells and Prevented Graft-Versus-Host Diseases

• Published in: Cell Transplantation Vol. 18; no. 5-6; pp. 627 - 638
• Main Authors: Kitazawa, Yusuke, Fujino, Masayuki, Li, Xiao-Kang, Xie, Lin, Ichimaru, Naotsugu, Okumi, Masayoshi, Nonomura, Norio, Tsujimura, Akira, Isaka, Yoshitaka, Kimura, Hiromitsu, Hünig, Thomas, Takahara, Shiro
• Format: Book Review Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.05.2009; SAGE Publishing
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; CD28 Antigens - immunology; Cell Proliferation; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Graft vs Host Disease - immunology; Graft vs Host Disease - prevention & control; Interferon-gamma - genetics; Interferon-gamma - metabolism; Interleukin-10 - genetics; Interleukin-10 - metabolism; Interleukin-2 - genetics; Interleukin-2 - metabolism; Interleukin-4 - genetics; Interleukin-4 - metabolism; Male; Rats; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Graft-versus-host disease; nTreg; Superagonist CD28 antibody; Treg
• ISSN: 0963-6897; 1555-3892
• DOI: 10.1177/096368970901805-619

Regulatory lymphocytes play a pivotal role in preventing organ-specific autoimmune disease and in induction and maintenance of tolerance in various experimental transplantation models. The enhancement of the number and activity of peripheral CD4+CD25+ Treg cells is an obvious goal for the treatment of autoimmunity and for the suppression of alloreactions. The present study demonstrates that naturally occurring CD4+CD25+ Treg (nTreg) cells preferentially proliferate to a fourfold increase within 3 days in response to the administration of a single superagonistic CD28-specific monoclonal antibody (supCD28 mAb). The appearance of increased Foxp3 molecules was accompanied with polarization toward a Th2 cytokine profile with decreased production of IFN-γ and increased production of IL-4 and IL-10 in the expanded Treg subset. Adoptive transfer of supCD28 mAb-expanded cells in a graft-versus-host disease (GvHD) model induced a potent inhibition of lethality. These results suggest that this therapeutic effect is mediated by the in vivo expansion of nTreg cells. Taken together, these data demonstrate that supCD28-mAb may target nTreg cells in vivo and maintain and enhance their potent regulatory functions for the treatment GvHD.