Among stroke patients, plasma soluble PrP<sup>C</sup> was positively associated with Th2 proportion (ρ = 0.73; P < 0.001) and negatively associated with the Th1/Th2 ratio (ρ = -0.66; P < 0.001); both associations remained significant after covariate adjustment (Th2: B = 1.504, 95% CI 1.166-1.841; Th1/Th2: B = -2.374, 95% CI -3.427--1.322; both P < 0.001).<h4>Conclusions</h4>Plasma soluble PrP<sup>C</sup> is elevated early after ischemic stroke and is associated with stroke severity and a Th2-skewed circulating CD4<sup>+</sup> T-cell profile. Here, CD4 is linked to Stroke.