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Activated human CD25+B cells are able to induce cell cycle arrest and apoptosis in CD4+T‐Helper cells
Author(s) -
Tretter Theresa,
Venigalla Ram Kumar,
Eckstein Volker,
Saffrich Rainer,
HannsMartin Lorenz
Publication year - 2008
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.22.1_supplement.848.33
Subject(s) - il 2 receptor , cd28 , cd19 , apoptosis , microbiology and biotechnology , t cell , cd40 , interleukin 21 , cytokine , biology , b cell , cd3 , cytotoxic t cell , chemistry , immunology , antigen , flow cytometry , cd8 , in vitro , immune system , antibody , biochemistry
B cells play an important role as APC. However several hints indicating an additional regulatory role remain to be elucidated Methods : CD19+B and CD4+T cells were separated from human PBMC by MACS. B cells were prestimulated with SAC or αIgM/IgG, irradiated and cocultured with CD4+T cells and αCD3+IL‐2 or αCD3+αCD28. T cell proliferation was determined by 3 H Thymidine incorporation or PKH‐26 and apoptosis by AnnexinV Results : T cell proliferation and cytokine production (IL‐10, IFNg) under optimal stimulatory conditions was inhibited by more than 70% in presence of preactivated, FACS‐sorted, large CD25+B cells vs. small CD25‐B cells. Suppression was strictly dependent on cell‐contact and constant presence of B cells as determined by cell culture inserts and reconstitution of cell division after removal from B cells. Blocking IL‐2Rα/β on B cells abolished suppression by about 50%, as did decreasing concentrations of IL‐2, suggesting that B cell suppressor activity is determined by the amount of IL‐2 available. Further, B cells induced apoptosis in a subpopulation of T cells (37% vs 17% after 24h) independent from blocking the CD95‐CD95L pathway Conclusions : Polyclonally activated CD25+B cells are able to costimulate or suppress T cell mediated responses, depending on activation status and environmental conditions. Future experiments deal with the mechanisms behind and their pathophysiological impact.