Evidence for an underlying CD4 helper and CD8 T-cell defect in B-cell-deficient mice:: Failure to clear persistent virus infection after adoptive immunotherapy with virus-specific memory cells from μMT/μMT mice
Evidence for an underlying CD4 helper and CD8 T-cell defect in B-cell-deficient mice:: Failure to clear persistent virus infection after adoptive immunotherapy with virus-specific memory cells from μMT/μMT mice
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DOI：
10.1128/jvi.72.11.9208-9216.1998
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发表时间：
1998-11-01
影响因子：
5.4
通讯作者：
Oldstone, MBA
中科院分区：
文献类型：
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作者：
Homann, D;Tishon, A;Oldstone, MBA
病毒特异性记忆淋巴细胞的连续转移可用于鉴定参与清除持续性病毒感染的因素和机制。为了分析B细胞在清除淋巴细胞性脉络丛脑膜炎病毒（LCMV）持续感染中的作用，我们使用B细胞缺陷的μ MT/μ MT（B-/-）小鼠，B-/-小鼠通过病毒特异性、主要组织相容性复合体（MIIC）I类限制性CD 8（+）细胞毒性T淋巴细胞（CTL）以与B细胞活性（B+/+）小鼠相同的动力学和效率控制急性LCMV感染，来自B-/-和B+/+小鼠的CTL在与已知LCMV CTL表位的亲和力方面是等同的，并且具有相似的CTL前体频率（pCTL），来自B+/+小鼠的记忆细胞的连续转移导致来自持续感染的B+/+受体的病毒清除，即使在体外耗尽B细胞之后，这表明在转移群体中不需要B细胞或免疫球蛋白。相反，从B-/-小鼠移植记忆脾细胞不能清除病毒。通过转移更高数量的pCTL或通过用LCMV免疫B细胞或免疫血清补充B-/-记忆脾细胞都不能恢复对病毒的控制。相反，发现B-/-小鼠具有严重的CD 4辅助细胞缺陷。此外，与来自B+/+小鼠的培养的脾细胞相比，来自B-/-小鼠的脾细胞分泌较少的γ干扰素（IFN-γ）和白细胞介素2，其中CD 8 T细胞的差异最明显。虽然强调了CD 4 T辅助细胞和IFN-γ在控制持续感染中的重要性，但B-/-小鼠中的CD 4 T辅助细胞和CD 8 T细胞缺陷表明B细胞有助于诱导感受态T效应细胞。
Adoptive transfer of virus-specific memory lymphocytes can be used to identify factors and mechanisms involved in the clearance of persistent virus infections. To analyze the role of B cells in clearing persistent infection with lymphocytic choriomeningitis virus (LCMV), we used B-cell-deficient mu MT/mu MT (B-/-) mice, B-/- mice controlled an acute LCMV infection with the same kinetics and efficiency as B-cell-competent (B+/+) mice via virus-specific, major histocompatibility complex (MIIC) class I restricted CD8(+) cytotoxic T lymphocytes (CTL), CTL from B-/- and B+/+ mice were equivalent in affinity to known LCMV CTL epitopes and had similar CTL precursor frequencies (pCTL), Adoptive transfer of memory cells from B+/+ mice led to virus clearance from persistently infected B+/+ recipients even after in vitro depletion of B cells, indicating that B cells or immunoglobulins are not required in the transfer population. In contrast, transfer of memory splenocytes from B-/- mice Failed to clear virus. Control of virus was restored neither by transferring higher numbers of pCTL nor by supplementing B-/- memory splenocytes with LCMV-immune B cells or immune sera. Instead, B-/- mice were found to have a profound CD4 helper defect, Furthermore, compared to cultured splenocytes from B+/+ mice, those from B-/- mice secreted less gamma interferon (IFN-gamma) and interleukin 2, with differences most pronounced for CD8 T tells. While emphasizing the importance of CD4 T-cell help and IFN-gamma in the control of persistent infections, the CD4 T-helper and CD8 T-cell defects in B-/- mice suggest that B cells contribute to the induction of competent T effector cells.