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CUTTING EDGE |
* Department of Microbiology and Immunology, Dartmouth Medical School and Norris Cotton Cancer Center, Lebanon, NH 03756; and
Department of Experimental Pathology, Institute for Frontier Medical Sciences, and Department of Transplantation and Immunology, Faculty of Medicine, Kyoto University, Kyoto, Japan
CD4+CD25+ regulatory T cells (Treg) are potent immunosuppressive cells that are pivotal in the regulation of peripheral tolerance. In this report, we identify granzyme B (GZ-B) as one of the key components of Treg-mediated suppression. Induction of regulatory activity is correlated with the up-regulation of GZ-B expression. Proof of a functional involvement of GZ-B in contact-mediated suppression by Treg is shown by the reduced ability of Treg from GZ-B–/– mice to suppress as efficiently as Treg from WT mice. GZ-B-mediated suppression is perforin independent, because suppression by Treg from perforin–/– and WT is indistinguishable. Additionally, suppression mediated by Treg appears to be mediated, in part, by the induction of apoptosis in the CD4+CD25– effector cell. In summary, GZ-B is one of the key mechanisms through which CD4+CD25+ Treg induce cell contact-mediated suppression.
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A. Y. Rudensky and D. J. Campbell In vivo sites and cellular mechanisms of T reg cell-mediated suppression J. Exp. Med., March 20, 2006; 203(3): 489 - 492. [Abstract] [Full Text] [PDF]
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S. Koonpaew, S. Shen, L. Flowers, and W. Zhang LAT-mediated signaling in CD4+CD25+ regulatory T cell development J. Exp. Med., January 23, 2006; 203(1): 119 - 129. [Abstract] [Full Text] [PDF]
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J. Yang, S. P. Huck, R. S. McHugh, I. F. Hermans, and F. Ronchese Perforin-dependent elimination of dendritic cells regulates the expansion of antigen-specific CD8+ T cells in vivo PNAS, January 3, 2006; 103(1): 147 - 152. [Abstract] [Full Text] [PDF]
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