The spleen CD4+ T cell response to blood-stage Plasmodium chabaudi malaria develops in two phases characterized by different properties.
The spleen CD4+ T cell response to blood-stage Plasmodium chabaudi malaria develops in two phases characterized by different properties.
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DOI：
10.1371/journal.pone.0022434
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Lima MR
中科院分区：
文献类型：
--
作者：
Muxel SM;Freitas do Rosário AP;Zago CA;Castillo-Méndez SI;Sardinha LR;Rodriguez-Málaga SM;Câmara NO;Álvarez JM;Lima MR
脾脏CD 4 + T细胞在疟疾发病机制和保护性免疫的发展中起着关键作用，因此有必要深入了解疟原虫感染期间其激活和调节的机制。在此，我们详细研究了非常规和常规脾CD 4 + T细胞在夏氏疟原虫疟疾期间的行为。我们利用了这样一个事实，即在CD 1d-/-小鼠中产生的大部分CD 4 + T细胞是I-Ab限制性的（常规细胞），而在I-Ab-/-小鼠中它们的对应物受到CD 1d和其他IB类主要组织相容性复合体（MHC）分子的限制（非常规细胞）。我们发现，传统的CD 4 + T细胞是对感染的免疫反应的主要参与者，这种免疫反应伴随着急性和慢性寄生虫血症在两个连续的阶段中发展。常规CD 4 + T细胞应答的早期阶段是强烈的且持续时间短，快速提供大量促炎细胞因子并帮助滤泡和边缘区B细胞分泌多克隆免疫球蛋白。TNF-α和IFN-γ的产生主要依赖于常规的CD 4 + T细胞。IFN-γ由非常规和常规CD 4 + T细胞同时产生。免疫应答的早期阶段在感染一周后结束，大部分CD 4 + T细胞被清除，这为获得性免疫的发展提供了机会。出乎意料的是，CD 1d限制性CD 4 + T细胞的主要贡献发生在反应的第二阶段开始时，但不是更早，有助于IFN-γ和寄生虫特异性抗体的产生。我们的结论是，传统的CD 4 + T细胞在夏氏疟原虫疟疾发病时起着核心作用，与非传统的CD 4 + T细胞平行作用，作为先天性和获得性免疫之间的联系。这项研究有助于了解疟疾免疫学，并为未来旨在破译疟原虫感染免疫反应背后的分子机制的研究开辟了前景。
The pivotal role of spleen CD4+ T cells in the development of both malaria pathogenesis and protective immunity makes necessary a profound comprehension of the mechanisms involved in their activation and regulation during Plasmodium infection. Herein, we examined in detail the behaviour of non-conventional and conventional splenic CD4+ T cells during P. chabaudi malaria. We took advantage of the fact that a great proportion of CD4+ T cells generated in CD1d-/- mice are I-Ab-restricted (conventional cells), while their counterparts in I-Ab-/- mice are restricted by CD1d and other class IB major histocompatibility complex (MHC) molecules (non-conventional cells). We found that conventional CD4+ T cells are the main protagonists of the immune response to infection, which develops in two consecutive phases concomitant with acute and chronic parasitaemias. The early phase of the conventional CD4+ T cell response is intense and short lasting, rapidly providing large amounts of proinflammatory cytokines and helping follicular and marginal zone B cells to secrete polyclonal immunoglobulin. Both TNF-α and IFN-γ production depend mostly on conventional CD4+ T cells. IFN-γ is produced simultaneously by non-conventional and conventional CD4+ T cells. The early phase of the response finishes after a week of infection, with the elimination of a large proportion of CD4+ T cells, which then gives opportunity to the development of acquired immunity. Unexpectedly, the major contribution of CD1d-restricted CD4+ T cells occurs at the beginning of the second phase of the response, but not earlier, helping both IFN-γ and parasite-specific antibody production. We concluded that conventional CD4+ T cells have a central role from the onset of P. chabaudi malaria, acting in parallel with non-conventional CD4+ T cells as a link between innate and acquired immunity. This study contributes to the understanding of malaria immunology and opens a perspective for future studies designed to decipher the molecular mechanisms behind immune responses to Plasmodium infection.
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影响因子：
56.9
作者：
GRUSBY, MJ;JOHNSON, RS;GLIMCHER, LH
通讯作者：
GLIMCHER, LH
影响因子：
3.1
作者：
Li, C;Corraliza, I;Langhorne, J
通讯作者：
Langhorne, J
影响因子：
4.4
作者：
LIMA, MRD;BANDEIRA, A;COUTINHO, A
通讯作者：
COUTINHO, A
影响因子：
3.1
作者：
Helmby, H;Jönsson, G;Troye-Blomberg, M
通讯作者：
Troye-Blomberg, M
DOI：
10.1073/pnas.0809742106
发表时间：
2009-04-07
影响因子：
11.1
作者：
Franklin, Bernardo S.;Parroche, Peggy;Gazzinelli, Ricardo T.
通讯作者：
Gazzinelli, Ricardo T.