Immune suppression or enhancement by CD137 T cell costimulation during acute viral infection is time dependent
J. Clin. Invest. Benyue Zhang, et al. 117:3029 doi:10.1172/JCI32426 [Go to this article.]

Figure 1
Anti-CD137 mAbs suppress antiviral immunity. An acute viral infection was generated in C57BL/6 mice by injecting 2 × 10⁵ PFU LCMV Armstrong i.p. followed by injection of 200 μg α-CD137 (clone 3H3) or rat IgG by i.p. on day 1 P.I. (A) Reduction in virus-specific T cell–dependent humoral immunity on days 8 and 30 P.I. (B) Marked reduction in the number of virus-specific antibody-secreting cells in bone marrow at day 30 P.I. (C) CD4⁺ T cells were unable to produce IFN-γ following in vitro peptide restimulation with CD4-restricted immunodominant LCMV-derived peptides on day 8 P.I. (D) On day 8 P.I. antiviral CD8⁺ T cell expansion was determined by D^bNP396-404 tetramer staining and CD43 upregulation on virus-activated T cells. (E) Absolute numbers of NP396-404⁺ CD8⁺ T cells were enumerated following FACS analysis of tetramer-stained T cells. (F) IFN-γ staining was measured following in vitro NP396-404 peptide restimulation and ICS with a FITC-conjugated anti–IFN-γ mAb. (G) CTL responses against NP396-404 peptide–pulsed MC57 cells were measured ex vivo from naive mice (lines), LCMV-infected anti-CD137–injected mice (diamonds), LCMV-infected rat IgG–injected mice (circles), and LCMV-infected untreated mice (squares). E:T, effector to target ratio. Data are from 1 representative experiment of 3. (H) LCMV-specific CD8⁺ T cell responses to immunodominant epitopes were 10⁵ IFN-γ⁺ T cells/spleen, subdominant epitopes were 10⁴ IFN-γ⁺ T cells/spleen on day 30 P.I. by measuring IFN-γ production in response to in vitro peptide restimulation, ICS, and FACS analysis.