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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >Protein Vaccines Induce Uncommitted IL-2-Secreting Human and Mouse CD4 T Cells, Whereas Infections Induce More IFN-{gamma}-Secreting Cells.
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Protein Vaccines Induce Uncommitted IL-2-Secreting Human and Mouse CD4 T Cells, Whereas Infections Induce More IFN-{gamma}-Secreting Cells.

机译：蛋白疫苗可诱导未定型的IL-2分泌人和小鼠CD4 T细胞，而感染则可诱导更多的IFN-γ分泌细胞。

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摘要

Mouse and human CD4 T cells primed during an immune response may differentiate into effector phenotypes such as Th1 (secreting IFN-gamma) or Th2 (secreting IL-4) that mediate effective immunity against different classes of pathogen. However, primed CD4 T cells can also remain uncommitted, secreting IL-2 and chemokines, but not IFN-gamma or IL-4. We now show that human CD4 T cells primed by protein vaccines mostly secreted IL-2, but not IFN-gamma, whereas in the same individuals most CD4 T cells initially primed by infection with live pathogens secreted IFN-gamma. We further demonstrate that many tetanus-specific IL-2(+)IFN-gamma(-) cells are uncommitted and that a single IL-2(+)IFN-gamma(-) cell can differentiate into Th1 or Th2 phenotypes following in vitro stimulation under appropriate polarizing conditions. In contrast, influenza-specific IL-2(+)IFN-gamma(-) CD4 cells maintained a Th1-like phenotype even under Th2-polarizing conditions. Similarly, adoptively transferred OTII transgenic mouse T cellssecreted mainly IL-2 after priming with OVA in alum, but were biased toward IFN-gamma secretion when primed with the same OVA peptide presented as a pathogen Ag during live infection. Thus, protein subunit vaccines may prime a unique subset of differentiated, but uncommitted CD4 T cells that lack some of the functional properties of committed effectors induced by infection. This has implications for the design of more effective vaccines against pathogens requiring strong CD4 effector T cell responses.
机译：在免疫应答过程中引发的小鼠和人类CD4 T细胞可能分化为效应子表型，例如Th1（分泌IFN-γ）或Th2（分泌IL-4），它们介导针对不同种类病原体的有效免疫力。但是，引发的CD4 T细胞也可以保持未定状态，分泌IL-2和趋化因子，但不分泌IFN-γ或IL-4。现在我们显示由蛋白质疫苗引发的人CD4 T细胞主要分泌IL-2，但不分泌IFN-γ，而在同一个体中，最初由活病原体感染引发的大多数CD4 T细胞分泌IFN-γ。我们进一步证明，许多破伤风特异性IL-2（+）IFN-γ（-）细胞是未犯的，并且单个IL-2（+）IFN-γ（-）细胞可以在体外分化为Th1或Th2表型在适当的极化条件下进行刺激。相反，即使在Th2极化条件下，流感特异性IL-2（+）IFN-γ（-）CD4细胞仍保持Th1样表型。类似地，过继转移的OTII转基因小鼠T细胞在明矾中用OVA引发后主要分泌IL-2，但是当在活体感染过程中用作为病原体Ag的相同OVA肽引发时，偏向IFN-γ分泌。因此，蛋白亚基疫苗可能引发了分化的但未定型的CD4 T细胞的独特子集，而该子集缺少某些感染引起的定型效应子的功能特性。这对于设计针对需要强CD4效应T细胞反应的病原体的更有效疫苗的设计具有重要意义。

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