Immunoproteasomes are essential for survival and expansion of T cells in virus-infected mice
Immunoproteasomes are essential for survival and expansion of T cells in virus-infected mice
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DOI：
10.1002/eji.201040620
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发表时间：
2010-12-01
影响因子：
5.4
通讯作者：
Basler, Michael
中科院分区：
文献类型：
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作者：
Moebius, Jacqueline;van den Broek, Maries;Basler, Michael
含有ifn诱导亚基β 1i （LMP2）、β 2i （MECL-1）和β 5i （LMP7）的免疫蛋白酶体改变蛋白酶体切割偏好，优化MHC I类分子肽配体的生成。在这里，我们报道了免疫蛋白酶体亚基在小鼠病毒感染期间对CD4（+）和CD8(+) T细胞存活和扩增的一种意想不到的新功能。免疫蛋白酶体亚单位缺乏对过继转移后t细胞存活的影响最为突出的是缺乏LMP7，其次是mcl -1和LMP2。T细胞在未感染小鼠中的存活或转移到rag2（-/-）小鼠后的稳态扩张不受缺乏免疫亚单位的影响。缺乏LMP7或mel -1的淋巴细胞性脉络丛脑膜炎病毒（LCMV）特异性CD8(+) T细胞在转移到LCMV感染的小鼠体内后开始分裂，但在转移后2天内经历了相当大的细胞损失。我们提供了强有力的证据，证明移植后免疫蛋白酶体缺陷T细胞的丢失不是宿主排斥的结果，而是基于lcmv感染小鼠中T细胞存活所需的免疫蛋白酶体。因此，免疫蛋白酶体可能有资格作为抑制不希望的促炎t细胞反应的潜在新靶点。
Immunoproteasomes containing the IFN-inducible subunits beta 1i (LMP2), beta 2i (MECL-1) and beta 5i (LMP7) alter proteasomal cleavage preference and optimize the generation of peptide ligands of MHC class I molecules. Here, we report on an unexpected new function of immunoproteasome subunits for the survival and expansion of CD4(+) and CD8(+) T cells during viral infection of mice. The effect of immunoproteasome subunit deficiency on T-cell survival upon adoptive transfer was most prominent for the lack of LMP7 followed by MECL-1 and LMP2. The survival of T cells in uninfected mice or the homeostatic expansion after transfer into RAG-2(-/-) mice was not affected by the lack of the immunosubunits. Lymphocytic choriomeningitis virus (LCMV)-specific CD8(+) T cells lacking LMP7 or MECL-1 started to divide after transfer into LCMV-infected mice but experienced a considerable cell loss within 2 days after transfer. We provide strong evidence that the loss of immunoproteasome-deficient T cells after transfer is not a consequence of graft rejection by the host, but instead is based on the requirement for immunoproteasomes for the survival of T cells in LCMV-infected mice. Therefore, the immunoproteasome may qualify as a potential new target for the suppression of undesired proinflammatory T-cell responses.