Blockage of CTLA-4, PD-1, and TIM-3 signaling during P. vivax infection enhances cytokine production. PBMCs from P. vivax–infected patients were cultured with P. vivax–infected reticulocytes (Pv-RET), uninfected reticulocytes (RET), medium alone, and anti-CD3/anti-CD28 (from left to right), in the absence (−) or presence of anti-CTLA-4 plus anti-PD-L1 plus TIM-3 blocking antibodies (CPT). Supernatant was collected after 96 hours of culture, and the levels of IFN-γ, IL-2, TNF-α, IL-4, and IL-10 were measured by cytometric bead array. Bars indicate mean values, and lines represent standard error from 12 patients pooled from 3 independent experiments (n = 12). **.001 < P < .01 and ***P < .001. Abbreviations: CTLA-4, cytotoxic T-lymphocyte attenuator-4; IFN, interferon; IL, interleukin; PBMCs, peripheral blood mononuclear cells; PD-1, programmed death-1; PD-L1, programmed death-ligand 1; TIM-3, T-cell immunoglobulin and mucin–3; TNF, tumor necrosis factor.