title: Dose-dependent induction of murine Th1/Th2 responses to sheep red blood cells occurs in two steps: antigen presentation during second encounter is decisive.
abstract: The differentiation of CD4 T cells into Th1 and Th2 cells in vivo is difficult to analyze since it is influenced by many factors such as genetic background of the mice, nature of antigen, and adjuvant. In this study, we used a well-established model, which allows inducing Th1 or Th2 cells simply by low (LD, 10(5)) or high dose (HD, 10(9)) injection of sheep red blood cells (SRBC) into C57BL/6 mice. Signature cytokine mRNA expression was determined in specific splenic compartments after isolation by laser-microdissection. LD immunization with SRBC induced T cell proliferation in the splenic T cell zone but no Th1 differentiation. A second administration of SRBC into the skin rapidly generated Th1 cells. In contrast, HD immunization with SRBC induced both T cell proliferation and immediate Th2 differentiation. In addition, splenic marginal zone and B cell zone were activated indicating B cells as antigen presenting cells. Interestingly, disruption of the splenic architecture, in particular of the marginal zone, abolished Th2 differentiation and led to the generation of Th1 cells, confirming that antigen presentation by B cells directs Th2 polarization. Only in its absence Th1 cells develop. Therefore, B cells might be promising targets in order to therapeutically modulate the T cell response.
authors.affiliation: Center for Structural and Cell Biology in Medicine, Institute of Anatomy, University of Lübeck, Lübeck, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Stamm
authors.forename: Julia
authors.initials: J
authors.lastname: Barthelmann
authors.forename: Natalia
authors.initials: N
authors.lastname: Kunz
authors.forename: Kai-Michael
authors.initials: KM
authors.lastname: Toellner
authors.forename: Jürgen
authors.initials: J
authors.lastname: Westermann
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kalies
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012756:Sheep / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000941:Antigens; D016207:Cytokines