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- Title
Activated CD4<sup>+</sup> T cells enter the splenic T-cell zone and induce autoantibody-producing germinal centers through bystander activation.
- Authors
Banczyk, David; Kalies, Kathrin; Nachbar, Lars; Bergmann, Lars; Schmidt, Philipp; Bode, Ulrike; Teegen, Bianca; Steven, Philipp; Lange, Tanja; Textor, Johannes; Ludwig, Ralf J.; Stöcker, Winfried; König, Peter; Bell, Eric; Westermann, Jürgen
- Abstract
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.
- Publication
European Journal of Immunology, 2014, Vol 44, Issue 1, p93
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201343811