Fig. 4
From: CXCR5+PD-1+ follicular helper CD8 T cells control B cell tolerance
Increased autoantibody production by CD8+ T-cell-specific deletion of Stat5. a GC B-cell generation in CD4+ T-cell-depleted Stat5fl/−CD8Cre mice. CD4+ T-cell-depleted Stat5+/+CD8Cre and Stat5fl/−CD8Cre mice were infected with LCMV and analyzed 14 days later. The experimental scheme is shown (upper). Dot plots show percentages of Fas+GL7+ cells in the gated B220+ population. Each dot represents an individual mouse and horizontal bars indicate mean values (lower). Mean ± SD is shown. b The serum levels of LCMV-specific IgG and IgG2a in CD4+ T-cell-depleted Stat5+/+CD8Cre and Stat5fl/−CD8Cre mice. Each dot represents an individual mouse and horizontal bars indicate mean values. Mean ± SD is shown. c Markedly increased autoantibodies in CD4+ T-cell-depleted Stat5fl/−CD8Cre mice following acute LCMV infection. Following LCMV infection, the sera from CD4+ T-cell-depleted mice were screened by the autoantigen array. d Increased GC localization of CD8 T-cells in Stat5-deficient mice. The spleen sections from LCMV-infected Stat5+/+CD8CreYFP or Stat5fl/−CD8CreYFP mice were stained with antibodies against B220 (red), GL7 (white) and CXCR5 (blue), and imaged using the Nikon Inverted Microscope. The examples of YFP+ CD8 T cells in GC were pointed out by the white arrows. Data shown are representative of three Stat5+/+CD8CreYFP and two Stat5fl/−CD8CreYFP mice. Scale bars, 100 μm. e Promoting B cells to produce autoantibodies by CD8 T cells in vivo. CD8 T cells sorted from LCMV-infected wild-type mice were adoptively transferred into Rag1-deficient mice with B cells. The recipients were infected with LCMV and 2 months later, anti-nuclear antibodies (ANA) were measured. Each dot represents the level of ANA in an individual recipient before or after adoptive transfer of the indicated cells and horizontal bars indicate mean values. Mean ± SD is shown. Statistical analysis was performed with the Mann–Whitney test (a) or the unpaired two-tailed Student’s t-test (b, e). Data shown are obtained from or representative of 8 (a, b), 6 (c) or 3 (d) Stat5+/+CD8Cre/ YFP and 11 (a, b), 9 (c) or 2 (d) Stat5fl/−CD8Cre/YFP mice. Source data are available as a source data file
