巴塞尔大学Daniel D. Pinschewer团队的一项最新研究揭示了围产期感染引发克隆限制性T滤泡辅助细胞反应，驱动抗体介导的病毒控制。相关论文于2026年3月30日发表在《免疫学》杂志上。

研究围产期淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染——新生儿抗病毒免疫耐受的原型母基模型，观察抗体介导的病毒载量抑制和典型生发中心（GC）反应。这种新生儿反应是由抗病毒CD4⁺ T滤泡辅助（Tfh）细胞反应驱动的。

然而，与成年感染小鼠相比，围产期感染动物体内的病毒表位特异性CD4⁺ T细胞数量较少，克隆多样性也较差。

此外，CD4⁺ T细胞补充增强了围产期感染小鼠的GC反应，而不是成年感染小鼠。因此，体液免疫防御部分不受新生儿耐受性的影响。更广泛地说，数字和克隆限制CD4⁺ Tfh反应使其成为功能性治愈的免疫治疗靶点。

研究人员表示，围产期感染通常导致病毒持续存在，如在人类中观察到的乙型肝炎病毒。通常认为，持久性与免疫耐受性有关，但这并不能预测抗病毒抗体的出现和最终的病毒载量控制。

附：英文原文

Title: Perinatal infection elicits clonally restricted T follicular helper cell responses that drive antibody-mediated viral control

Author: Katrin Martin, Peter Reuther, Florian Geier, Anna-Friederike Marx, Tiago Abreu-Mota, Jonas Fixemer, Anna Lena Kastner, Weldy V. Bonilla, Karen Tintignac, Karsten Stauffer, Min Lu, Dominik Schuler, Ingrid Wagner, Doron Merkler, Daniel D. Pinschewer

Issue&Volume: 2026-03-30

Abstract: Perinatal infection often results in viral persistence, as observed for hepatitis B virus in humans. Commonly held concepts suggest that persistence is associated with immunotolerance, but this fails to predict the emergence of antiviral antibodies and eventual viral load control. Studying perinatal lymphocytic choriomeningitis virus (LCMV) infection, the prototypic mouse model of neonatal antiviral immunotolerance, we observe antibody-mediated viral load suppression and canonical germinal center (GC) reactions. This neonatal response is driven by antiviral CD4+ T follicular helper (Tfh) cell responses. However, viral epitope-specific CD4+ T cells in perinatally infected animals are less abundant and less clonally diverse than in adult-infected mice. Furthermore, CD4+ T cell supplementation augments GC responses in perinatally, but not adult, infected mice. Hence, humoral immune defense is partially exempt from neonatal tolerance. More broadly, the numerically and clonally restricted CD4+ Tfh response lends itself as an immunotherapeutic target for a functional cure.

DOI: 10.1016/j.immuni.2026.03.004

Source: https://www.cell.com/immunity/abstract/S1074-7613(26)00115-9