Phenotypic and functional profiling of malaria-induced CD8 and CD4 T cells during blood-stage infection with Plasmodium yoelii

Phenotypic and functional profiling of malaria-induced CD8 and CD4 T cells during blood-stage infection with Plasmodium yoelii
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DOI:
10.1111/j.1365-2567.2010.03363.x
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发表时间:
2011-02-01
期刊:
影响因子:
6.4
通讯作者:
Chauhan, Virander S.
Chauhan, Virander S.
中科院分区:
医学2区
文献类型:
--
作者:
Chandele, Anmol;Mukerjee, Paushali;Chauhan, Virander S.

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人们普遍认为抗体和CD4 T细胞在疟疾血液阶段的免疫反应中起关键作用,而CD8 T细胞的作用仍存在争议。在这里,我们发现CD8和CD4 T细胞对急性自限性血液期约氏疟原虫感染都有强烈的反应。与抗原特异性T细胞类似,CD8和CD4 T细胞均动态表达表面蛋白白介素(IL)-7R和程序性死亡-1 (PD-1)。此外,活化的CD8 T细胞在杀伤细胞凝集素样受体G1、l -选择素和B细胞淋巴瘤-2的表达上存在差异,并产生颗粒酶B,表明细胞毒性活性,而T-box转录因子TBX21在疟疾活化的CD4 T细胞中最初的高表达表明早期的T辅助型1 (Th1)偏斜免疫反应。我们的数据表明,血液期疟疾感染会导致惊人的T细胞反应,激活的CD8和CD4 T细胞具有与传统抗原特异性效应和记忆T细胞一致的表型和功能特征。因此,更好地了解血期感染诱导的CD8和CD4 t细胞反应可能对开发针对疟原虫红细胞期的疫苗至关重要。
P>It is widely accepted that antibodies and CD4 T cells play critical roles in the immune response during the blood stage of malaria, whereas the role of CD8 T cells remains controversial. Here, we show that both CD8 and CD4 T cells robustly responded to an acute self-limiting blood-stage infection with Plasmodium yoelii. Similar to antigen-specific T cells, both CD8 and CD4 T cells showed dynamic expression of the surface proteins interleukin (IL)-7R and programmed death-1 (PD-1). Additionally, activated CD8 T cells showed differences in the expression of Killer cell lectin-like receptor G1, L-selectin and B cell lymphoma-2 and produced granzyme B, indicating cytotoxic activity, and the initially high expression of T-box transcription factor TBX21 in malaria-activated CD4 T cells indicated an early T helper type 1 (Th1)-skewed immune response. Our data demonstrate that blood-stage malaria infection results in a striking T-cell response and that activated CD8 and CD4 T cells have phenotypic and functional characteristics that are consistent with conventional antigen-specific effector and memory T cells. Therefore, a better understanding of the CD8 and CD4 T-cell response induced by blood-stage infection may prove to be essential in the development of a vaccine that targets the erythrocytic stage of the malarial parasite.