T cell depletion or cytokine blockade abrogates the effects of CTLA-4 and PD-L1 blockade in <i>PbA</i>-infected BALB/c mice.

<p>BALB/c mice were infected i.v. with 10⁴<i>PbA</i> pRBCs and were treated with (<b>A,C</b>) α-CTLA or (<b>B,D</b>) α-PD-L1 antibodies. (<b>A,B</b>) CTLA-4 or PD-L1 blockade without T cell depletion (□,▪); with α-CD8 depletion throughout infection (▽,▾); with α-CD8 depletion early in infection (△,▴); with α-CD4 depletion throughout infection (◊, ⧫); or with α-CD4 depletion early in infection (○,•). Cumulative survival curves (left) and cumulative incidence of ECM (right). (<b>C,D</b>) CTLA-4 or PD-L1 blockade without cytokine blockade (□,▪) or with α-IFN-γ () or α-TNF () treatment on on days −1, 1, 3, 5 and 7. Cumulative survival curves (left) and cumulative incidence of ECM (right). Data are representative of two independent experiments performed with four mice in each group. P values: Log-rank (Mantel Cox) test for the survival curves, and Fisher's exact test for cumulative ECM incidence. Bonferroni correction was used to adjust for multiple comparisons; threshold for significance is P<0.01 for the T cell depletions and P<0.017 for the cytokine neutralisations.