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

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-g-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, from GZ-B-/- mice to suppress as efficiently as T-reg from W/T mice. GZ-B-mediated suppression is perform independent, because suppression by T-reg from perforin(-/-) and WT is indistinguishable. Additionally, suppression mediated by T-reg appears to be mediated, inpart, 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.