TY - JOUR
T1 - Enteroantigen-presenting B cells efficiently stimulate CD4(+) T cells in vitro
AU - Schmidt, Esben Gjerløff Wedebye
AU - Kristensen, Nanna Ny
AU - Claesson, Mogens Helweg
AU - Pedersen, Anders Elm
N1 - Copyright © 2010 Crohn's & Crohn's & Colitis Foundation of America, Inc.
PY - 2011/1
Y1 - 2011/1
N2 - Background: Presentation of enterobacterial antigens by antigen-presenting cells and activation of enteroantigen-specific CD4+ T cells are considered crucial steps in inflammatory bowel disease (IBD) pathology. The detrimental effects of such CD4+ T cells have been thoroughly demonstrated in models of colitis. Also, we have previously established an in vitro assay where murine enteroantigen-specific colitogenic CD4 +CD25- T cells are activated by splenocytes pulsed with an enterobacterial extract. Methods: CD4+CD25- T cells were stimulated in vitro with various kinds of enterobacterial extract-pulsed antigen-presenting cells. T-helper phenotypes were detected by flow cytometry. Results: We found that enteroantigen-pulsed splenic B cells possess a significantly higher and more sustained T cell stimulatory capacity than similarly pulsed splenic dendritic cells (DCs) measured by the level of enteroantigen-specific CD4+CD25- T cell proliferation. In support of this, we observed upregulation of classic maturation markers in B cells following incubation with enterobacterial antigens. Peritoneal and mesenteric lymph node-derived B cells were equally effective as enteroantigen-presenting stimulator cells. B cells greatly expanded the number of stimulated CD4+ T cells, which acquired a TH2 phenotype. Interestingly, regulatory T cells were primarily activated by enteroantigen-pulsed B cells but not by similarly pulsed DCs. Conclusions: We conclude that B cells are superior stimulators of enteroantigen-specific CD4+ T cells in vitro, favoring TH2 polarization. Thus, enteroantigen-processing and -presentation by B cells instead of by DCs might have opposing consequences for IBD development.
AB - Background: Presentation of enterobacterial antigens by antigen-presenting cells and activation of enteroantigen-specific CD4+ T cells are considered crucial steps in inflammatory bowel disease (IBD) pathology. The detrimental effects of such CD4+ T cells have been thoroughly demonstrated in models of colitis. Also, we have previously established an in vitro assay where murine enteroantigen-specific colitogenic CD4 +CD25- T cells are activated by splenocytes pulsed with an enterobacterial extract. Methods: CD4+CD25- T cells were stimulated in vitro with various kinds of enterobacterial extract-pulsed antigen-presenting cells. T-helper phenotypes were detected by flow cytometry. Results: We found that enteroantigen-pulsed splenic B cells possess a significantly higher and more sustained T cell stimulatory capacity than similarly pulsed splenic dendritic cells (DCs) measured by the level of enteroantigen-specific CD4+CD25- T cell proliferation. In support of this, we observed upregulation of classic maturation markers in B cells following incubation with enterobacterial antigens. Peritoneal and mesenteric lymph node-derived B cells were equally effective as enteroantigen-presenting stimulator cells. B cells greatly expanded the number of stimulated CD4+ T cells, which acquired a TH2 phenotype. Interestingly, regulatory T cells were primarily activated by enteroantigen-pulsed B cells but not by similarly pulsed DCs. Conclusions: We conclude that B cells are superior stimulators of enteroantigen-specific CD4+ T cells in vitro, favoring TH2 polarization. Thus, enteroantigen-processing and -presentation by B cells instead of by DCs might have opposing consequences for IBD development.
U2 - 10.1002/ibd.21429
DO - 10.1002/ibd.21429
M3 - Journal article
C2 - 20722062
SN - 1078-0998
VL - 17
SP - 308
EP - 318
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
IS - 1
ER -