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Incompletely activated CD4+ T cells induce granzyme B+ regulatory B cells in an interleukin 21‐dependent manner
Author(s) -
Dahlke Karen,
Hagn Magdalena,
Sontheimer Kai,
Beyer Thamara,
Lunov Oleg,
Fabricius Dorit,
Tron Kyrylo,
Nienhaus G. Ulrich,
Simmet Thomas,
Jahrsdörfer Bernd
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb507
Subject(s) - granzyme b , microbiology and biotechnology , granzyme , immune system , t cell , cytotoxic t cell , biology , immunology , perforin , cd8 , in vitro , biochemistry
Immune regulation is central for the development of an efficient cellular immune response. Both Treg cells and plasmacytoid DC can suppress T cell proliferation in a granzyme B (GzmB)‐dependent manner. In the present study we found that, depending on stimulation with interleukin (IL−) 21, B cells (BC) can also express GzmB and suppress T cell proliferation. GzmB expression in BC is enhanced by BC receptor engagement, and is suppressed by CD40 ligation. Since CD4+ T cells are a main source of IL‐21, we tested whether they can induce GzmB in BC. We found that incompletely activated CD4+ T cells, but not fully activated T cells can induce GzmB in co‐cultured BC. Using confocal microscopy, we showed that BC‐derived GzmB is enzymatically active and that GzmB+ BC transfer GzmB to CD4+ T cells. Furthermore, GzmB+ BC decreased CD4+ T cell expression of the TCR‐zeta chain, a GzmB target, which is required for T cell proliferation. Our results suggest BC may regulate cellular adaptive immune responses by Treg cell‐like mechanisms. Inhibition of BC‐derived GzmB may represent a novel strategy to induce more effective and comprehensive cellular immune responses.