Nikin-Beers Ryan, Ciupe Stanca M
Department of Mathematics, Virginia Tech, Blacksburg, VA, USA.
Math Med Biol. 2018 Jun 13;35(2):257-272. doi: 10.1093/imammb/dqx002.
Cross-reactive T cell responses induced by a primary dengue virus infection may contribute to increased disease severity following heterologous infections with a different virus serotype in a phenomenon known as the original antigenic sin. In this study, we developed and analyzed in-host models of T cell responses to primary and secondary dengue virus infections that considered the effect of T cell cross-reactivity in disease enhancement. We fitted the models to published patient data and showed that the overall infected cell killing is similar in dengue heterologous infections, resulting in dengue fever and dengue hemorrhagic fever. The contribution to overall killing, however, is dominated by non-specific T cell responses during the majority of secondary dengue hemorrhagic fever cases. By contrast, more than half of secondary dengue fever cases have predominant strain-specific T cell responses with high avidity. These results support the hypothesis that cross-reactive T cell responses occur mainly during severe disease cases of heterologous dengue virus infections.
由初次登革病毒感染诱导的交叉反应性T细胞应答，可能在一种称为原始抗原罪的现象中，导致在感染不同病毒血清型的异源感染后疾病严重程度增加。在本研究中，我们开发并分析了T细胞对初次和二次登革病毒感染应答的宿主内模型，该模型考虑了T细胞交叉反应性在疾病加重中的作用。我们将模型与已发表的患者数据进行拟合，结果表明，在登革热异源感染中，总体感染细胞杀伤情况相似，会导致登革热和登革出血热。然而，在大多数二次登革出血热病例中，对总体杀伤的贡献主要由非特异性T细胞应答主导。相比之下，超过一半的二次登革热病例具有高亲和力的主要毒株特异性T细胞应答。这些结果支持了以下假设：交叉反应性T细胞应答主要发生在异源登革病毒感染的严重疾病病例中。
