Cutting Edge: Contact-Mediated Suppression by CD4+CD25+ Regulatory Cells Involves a Granzyme B-Dependent, Perforin-Independent Mechanism1

By David C. Gondek, Li-Fan Lu, Sergio A. Quezada, Shimon Sakaguchi, R. Noelle. Journal of Immunology, 2005

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The PD-1 Pathway in Tolerance and Autoimmunity (2010, background): “(120) first demonstrated that granzyme B-deficient Tregs induced less effector cell apoptosis than wildtype Tregs.”
T Regulatory Cells: Key Players in Tumor Immune Escape and Angiogenesis (2012, background): “Tregs have been shown to exert cytolytic functions by using a variety of mediators, such as granzyme B (23, 24), the TRAIL”
Regulatory T Cells: Mechanisms of Differentiation and Function (2012, background): “Upon activation, Treg cells can kill either responder T cells or APCs in a granzyme B–dependent manner in vitro (224, 225).”
Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. (2007, background): “…B- and perforin-dependent fashion (Zhao et al., 2006), whereas Gondek et al. report that activated Immunity 27, 635–646, October 2007 ª2007 Elsevier Inc. 635 murine Treg cells suppressed CD4+CD25 T effector cells via a granzyme B-dependent, but perforin-independent, mechanism (Gondek et al., 2005).”
Mechanisms of foxp3+ T regulatory cell-mediated suppression. (2009, background): “…mouse Treg cells also results in upregulation of granzyme B expression and one report has claimed that Treg cells kill responder cells by a perforin-independent, granzyme B-dependent mechanisms (Gondek et al., 2005) and that granzyme B-deficient Treg cells had reduced suppressive activity in vitro.”