The +95C/A SNP in TLR3 associates with defective CD8⁺ T cells by peripheral DCs. Human CD141⁺ (BDCA-3⁺) DCs were isolated from peripheral blood of healthy volunteers bearing distinct TLR3 +95C/A genotypes (CC, CA, and AA) and were either left untreated or pulsed with poly(I:C), A fumigatus conidia, or fungal RNA. Relative expression of TLR3 (A) and type I IFNs (IFNA1 and IFNB1; B) was assessed by RT-PCR. (C) Frequencies of Ag-specific CD4⁺ or CD8⁺ T-cell clones were obtained by limiting dilution assays. Ag-specific proliferation of T-cell clones was assessed after coculture of responder CD4⁺ and CD8⁺ T cells with BDCA-3⁺ DCs pulsed with A fumigatus conidia or fungal RNA and measured by ³H-thymidine incorporation. Shown are the percentages of CD4⁺ or CD8⁺ T-cell clones/10⁶ cells. (D) Purified T-cell subsets were stimulated with 0.1% phytohemagglutinin in the presence of autologous PBMCs. DNA synthesis was measured by ³H-thymidine uptake (cpm, counts per minute). “None” indicates untreated DCs; and Ct, T cells alone. Data are mean values ± SD of at least 3 independent samples for each +95C/A genotype assessed in triplicate. *P < .05; **P < .01; and ***P < .001 for treated versus untreated (None) BDCA-3⁺ DCs.