Cutting edge: contact-mediated suppression by CD4+ CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism

DC Gondek, LF Lu, SA Quezada… - The journal of …, 2005 - journals.aai.org
The journal of immunology, 2005journals.aai.org
Abstract CD4+ CD25+ regulatory T cells (T reg) 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 T reg-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 T reg is shown by the reduced ability of T reg from
GZ-B−/− mice to suppress as efficiently as T reg from WT mice. GZ-B-mediated suppression …
Abstract
CD4+ CD25+ regulatory T cells (T reg) 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 T reg-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 T reg is shown by the reduced ability of T reg from GZ-B−/− mice to suppress as efficiently as T reg from WT mice. GZ-B-mediated suppression is perforin independent, because suppression by T reg from perforin−/− and WT is indistinguishable. Additionally, suppression mediated by T reg 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+ T reg induce cell contact-mediated suppression.
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