TY - JOUR
T1 - Activated CD4+ T cells enter the splenic T-cell zone and induce autoantibody-producing germinal centers through bystander activation
AU - Banczyk, David
AU - Kalies, Kathrin
AU - Nachbar, Lars
AU - Bergmann, Lars
AU - Schmidt, Philipp
AU - Bode, Ulrike
AU - Teegen, Bianca
AU - Steven, Philipp
AU - Lange, Tanja
AU - Textor, Johannes
AU - Ludwig, Ralf J.
AU - Stöcker, Winfried
AU - König, Peter
AU - Bell, Eric
AU - Westermann, Jürgen
PY - 2014/1/1
Y1 - 2014/1/1
N2 - CD4+ T (helper) cells migrate in huge numbers through lymphoid organs. However, little is known about traffic routes and kinetics of CD4+ T-cell subsets within different organ compartments. Such information is important because there are indications that CD4+ T cells may influence the function of microenvironments depending on their developmental stage. Therefore, we investigated the migration of resting (naïve), activated, and recently activated (memory) CD4+ T cells through the different compartments of the spleen. Resting and recently activated CD4+ T cells were separated from thoracic duct lymph and activated CD4+ T cells were generated in vitro by cross-linking the T-cell receptor and CD28. The present study shows that all three CD4+ T-cell subsets selectively accumulate in the T-cell zone of the spleen. However, only activated T cells induce the formation of germinal centers (GCs) and autoantibodies in rats and mice. Our results suggest that in a two-step process they first activate B cells independent of the T-cell receptor repertoire and CD40 ligand (CD154) expression. The activated B cells then form GCs whereby CD154-dependend T-cell help is needed. Thus, activated T cells may contribute to the development of autoimmune diseases by activating autoreactive B cells in an Ag-independent manner. European Journal of Immunology published by Wiley-VCH Verlag GmbH & Co. KGaA Weinheim.
AB - CD4+ T (helper) cells migrate in huge numbers through lymphoid organs. However, little is known about traffic routes and kinetics of CD4+ T-cell subsets within different organ compartments. Such information is important because there are indications that CD4+ T cells may influence the function of microenvironments depending on their developmental stage. Therefore, we investigated the migration of resting (naïve), activated, and recently activated (memory) CD4+ T cells through the different compartments of the spleen. Resting and recently activated CD4+ T cells were separated from thoracic duct lymph and activated CD4+ T cells were generated in vitro by cross-linking the T-cell receptor and CD28. The present study shows that all three CD4+ T-cell subsets selectively accumulate in the T-cell zone of the spleen. However, only activated T cells induce the formation of germinal centers (GCs) and autoantibodies in rats and mice. Our results suggest that in a two-step process they first activate B cells independent of the T-cell receptor repertoire and CD40 ligand (CD154) expression. The activated B cells then form GCs whereby CD154-dependend T-cell help is needed. Thus, activated T cells may contribute to the development of autoimmune diseases by activating autoreactive B cells in an Ag-independent manner. European Journal of Immunology published by Wiley-VCH Verlag GmbH & Co. KGaA Weinheim.
UR - https://www.scopus.com/pages/publications/84892446742
U2 - 10.1002/eji.201343811
DO - 10.1002/eji.201343811
M3 - Journal articles
C2 - 24114675
AN - SCOPUS:84892446742
SN - 0014-2980
VL - 44
SP - 93
EP - 102
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 1
ER -
SDG 3 – Gesundheit und Wohlergehen
SDG 9 – Industrie, Innovation und Infrastruktur