Mavrommatis Bettina, Baudino Lucie, Levy Prisca, Merkenschlager Julia, Eksmond Urszula, Donnarumma Tiziano, Young George, Stoye Jonathan, Kassiotis George
Retroviral Immunology, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, United Kingdom.
Retrovirus-Host Interactions, The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, United Kingdom; and.
J Immunol. 2016 Nov 1;197(9):3628-3638. doi: 10.4049/jimmunol.1600734. Epub 2016 Sep 19.
Elucidation of the immune requirements for control or elimination of retroviral infection remains an important aim. We studied the induction of adaptive immunity to neonatal infection with a murine retrovirus, under conditions leading to immunological tolerance. We found that the absence of either maternal or offspring adaptive immunity permitted efficient vertical transmission of the retrovirus. Maternal immunodeficiency allowed the retrovirus to induce central Th cell tolerance in the infected offspring. In turn, this compromised the offspring's ability to mount a protective Th cell-dependent B cell response. However, in contrast to T cells, offspring B cells were not centrally tolerized and retained their ability to respond to the infection when provided with T cell help. Thus, escape of retrovirus-specific B cells from deletional tolerance offers the opportunity to induce protective retroviral immunity by restoration of retrovirus-specific T cell help, suggesting similar T cell immunotherapies for persistent viral infections.
阐明控制或消除逆转录病毒感染的免疫需求仍然是一个重要目标。我们研究了在导致免疫耐受的条件下，对小鼠逆转录病毒新生儿感染的适应性免疫诱导情况。我们发现，母源或子代适应性免疫的缺失允许逆转录病毒高效垂直传播。母源免疫缺陷使逆转录病毒能够在受感染的子代中诱导中枢性Th细胞耐受。反过来，这损害了子代产生保护性Th细胞依赖性B细胞应答的能力。然而，与T细胞不同，子代B细胞未发生中枢性耐受，并且在获得T细胞帮助时保留了对感染作出反应的能力。因此，逆转录病毒特异性B细胞从缺失性耐受中逃逸，为通过恢复逆转录病毒特异性T细胞帮助来诱导保护性逆转录病毒免疫提供了机会，这表明针对持续性病毒感染有类似的T细胞免疫疗法。
