Protein Vaccines Induce Uncommitted IL-2-Secreting Human and Mouse CD4 T Cells, Whereas Infections Induce More IFN-γ-Secreting Cells1
Protein Vaccines Induce Uncommitted IL-2-Secreting Human and Mouse CD4 T Cells, Whereas Infections Induce More IFN-γ-Secreting Cells1
复制标题
蛋白质疫苗诱导未承诺的 IL-2 分泌人类和小鼠 CD4 T 细胞，而感染则诱导更多的 IFN-γ 分泌细胞1
作者：
A. Divekar;D. Zaiss;F. Lee;Dacheng Liu;D. Topham;A. Sijts;T. Mosmann
在免疫应答期间引发的小鼠和人CD 4 T细胞可以分化成效应子表型，例如Th 1（分泌IFN-γ）或Th 2（分泌IL-4），其介导针对不同类别病原体的有效免疫。然而，引发的CD 4 T细胞也可以保持未定型，分泌IL-2和趋化因子，但不分泌IFN-γ或IL-4。我们现在发现，由蛋白质疫苗引发的人CD 4 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CD 4 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−细胞是未定型的，并且单个IL-2+IFN-γ−细胞在适当的极化条件下体外刺激后可以分化为Th 1或Th 2表型。相比之下，流感特异性IL-2+IFN-γ− CD 4细胞即使在Th 2极化条件下也保持Th 1样表型。类似地，过继转移的OTII转基因小鼠T细胞在用明矾中的OVA引发后主要分泌IL-2，但当用在活感染期间作为病原体Ag呈递的相同OVA肽引发时偏向于IFN-γ分泌。因此，蛋白质亚单位疫苗可以引发分化的但未定型的CD 4 T细胞的独特子集，其缺乏由感染诱导的定型效应子的一些功能特性。这对设计更有效的疫苗对抗需要强CD 4效应T细胞应答的病原体具有意义。
Mouse and human CD4 T cells primed during an immune response may differentiate into effector phenotypes such as Th1 (secreting IFN-γ) 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-γ or IL-4. We now show that human CD4 T cells primed by protein vaccines mostly secreted IL-2, but not IFN-γ, whereas in the same individuals most CD4 T cells initially primed by infection with live pathogens secreted IFN-γ. We further demonstrate that many tetanus-specific IL-2+IFN-γ− cells are uncommitted and that a single IL-2+IFN-γ− cell can differentiate into Th1 or Th2 phenotypes following in vitro stimulation under appropriate polarizing conditions. In contrast, influenza-specific IL-2+IFN-γ− CD4 cells maintained a Th1-like phenotype even under Th2-polarizing conditions. Similarly, adoptively transferred OTII transgenic mouse T cells secreted mainly IL-2 after priming with OVA in alum, but were biased toward IFN-γ 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.
影响因子：
4.4
作者：
Nanki, T;Lipsky, PE
通讯作者：
Lipsky, PE
影响因子：
3.7
作者：
Chapman, TJ;Castrucci, MR;Topham, DJ
通讯作者：
Topham, DJ
影响因子：
15.9
作者：
Schultze, JL;Michalak, S;Nadler, LM
通讯作者：
Nadler, LM