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Tolerance induction in memory CD4 T cells is partial and reversible
bioRxiv - Immunology Pub Date : 2020-05-27 , DOI: 10.1101/2020.05.25.114785
Joshua I Gray , Shaima Al-Khabouri , Fraser Morton , Eric T Clambey , Laurent Gapin , Jennifer L Matsuda , John W Kappler , Philippa Marrack , Paul Garside , Thomas D Otto , Megan KL MacLeod

Memory T cells respond rapidly in part because they are less reliant on heightened levels of costimulatory molecules. This presents challenges to silencing memory T cells in tolerance strategies for autoimmunity or allergy. We find that memory CD4 T cells generated by infection or immunisation survive secondary activation with antigen delivered without adjuvant, regardless of their location in secondary lymphoid organs or peripheral tissues. These cells were, however, functionally altered following a tertiary immunisation with antigen and adjuvant, proliferating poorly but maintaining their ability to produce inflammatory cytokines. Transcriptional and cell cycle analysis of these memory CD4 T cells suggest they are unable to commit fully to cell division potentially because of low expression of DNA repair enzymes. In contrast, these memory CD4 T cells could proliferate following tertiary reactivation by viral re-infection. These data suggest that tolerance induction in memory CD4 T cells is partial and can be reversed.

中文翻译:

记忆CD4 T细胞中的耐受诱导是部分且可逆的

记忆T细胞反应迅速,部分原因是它们对共刺激分子水平的依赖性降低。这就提出了在自身免疫或过敏的耐受策略中沉默记忆T细胞的挑战。我们发现,由感染或免疫产生的记忆CD4 T细胞,无论其在次级淋巴器官或周围组织中的位置如何,都可以通过不带佐剂的抗原进行二次激活。但是,在用抗原和佐剂进行三次免疫后,这些细胞的功能发生了改变,增殖能力很差,但仍保持了它们产生炎性细胞因子的能力。这些记忆CD4 T细胞的转录和细胞周期分析表明,由于DNA修复酶的低表达,它们无法完全参与细胞分裂。相反,这些记忆性CD4 T细胞可通过病毒再感染在三次激活后增殖。这些数据表明记忆CD4 T细胞中的耐受诱导是部分的,可以逆转。
更新日期:2020-05-27
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