title: Activated CD4+ T cells enter the splenic T-cell zone and induce autoantibody-producing germinal centers through bystander activation.
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-dependent 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.
authors.affiliation: Center for Structural and Cell Biology in Medicine, Institute of Anatomy, University of Lübeck, Lübeck, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Banczyk
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kalies
authors.forename: Lars
authors.initials: L
authors.lastname: Nachbar
authors.forename: Lars
authors.initials: L
authors.lastname: Bergmann
authors.forename: Philipp
authors.initials: P
authors.lastname: Schmidt
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bode
authors.forename: Bianca
authors.initials: B
authors.lastname: Teegen
authors.forename: Philipp
authors.initials: P
authors.lastname: Steven
authors.forename: Tanja
authors.initials: T
authors.lastname: Lange
authors.forename: Johannes
authors.initials: J
authors.lastname: Textor
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Ludwig
authors.forename: Winfried
authors.initials: W
authors.lastname: Stöcker
authors.forename: Peter
authors.initials: P
authors.lastname: König
authors.forename: Eric
authors.initials: E
authors.lastname: Bell
authors.forename: Jürgen
authors.initials: J
authors.lastname: Westermann
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000378:metabolism*; D024201:Bystander Effect; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000235:genetics; D002478:Cells, Cultured; D018858:Germinal Center / Q000276:immunology*; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D023201:CD40 Ligand
keywords: Activated T cells; Development; Germinal center; Noncognate interaction; Rodent