Division of Infectious Diseases, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA.
J Immunol. 2013 Aug 1;191(3):1001-5. doi: 10.4049/jimmunol.1203520. Epub 2013 Jun 21.
Influenza-specific immunity in humans is unique because there are repeated exposures to viral strains containing genetically conserved epitopes recruiting memory CD4 T cells and novel epitopes stimulating naive CD4 T cells, possibly resulting in competition between memory and naive lymphocytes. In this study, we evaluated the effect of this competition on CD4 T cell and B cell response specificity using a murine model of sequential influenza infection. We found striking and selective decreases in CD4 T cell reactivity to nonconserved hemagglutinin (HA) epitopes following secondary influenza infection. Surprisingly, this shift in CD4 T cell specificity was associated with dramatic decreases in HA-specific Ab. These results suggest that repeated exposure to influenza viruses and vaccines containing conserved internal proteins may have unintended and negative consequences on the ability to induce HA-specific Ab to novel pandemic strains of influenza. These finding could have important implications on pandemic influenza preparedness strategies.
人类的流感特异性免疫是独特的，因为人体会反复接触到含有遗传上保守表位的病毒株，这些表位会招募记忆性 CD4 T 细胞，而新表位则会刺激幼稚 CD4 T 细胞，这可能导致记忆性和幼稚性淋巴细胞之间的竞争。在这项研究中，我们使用流感病毒的序贯感染的小鼠模型来评估这种竞争对 CD4 T 细胞和 B 细胞反应特异性的影响。我们发现，在二次流感感染后，针对非保守血凝素 (HA) 表位的 CD4 T 细胞反应性显著且具有选择性地下降。令人惊讶的是，CD4 T 细胞特异性的这种转变与 HA 特异性 Ab 的显著下降有关。这些结果表明，反复接触流感病毒和含有保守内部蛋白的疫苗可能会对诱导针对新型大流行性流感病毒株的 HA 特异性 Ab 的能力产生意想不到的负面影响。这些发现可能对大流行性流感的准备策略具有重要意义。
