Dataset Information

Circulating Th1-Cell-type Tfh Cells that Exhibit Impaired B Cell Help Are Preferentially Activated during Acute Malaria in Children.

ABSTRACT: Malaria-specific antibody responses are short lived in children, leaving them susceptible to repeated bouts of febrile malaria. The cellular and molecular mechanisms underlying this apparent immune deficiency are poorly understood. Recently, T follicular helper (Tfh) cells have been shown to play a critical role in generating long-lived antibody responses. We show that Malian children have resting PD-1(+)CXCR5(+)CD4(+) Tfh cells in circulation that resemble germinal center Tfh cells phenotypically and functionally. Within this population, PD-1(+)CXCR5(+)CXCR3(-) Tfh cells are superior to Th1-polarized PD-1(+)CXCR5(+)CXCR3(+) Tfh cells in helping B cells. Longitudinally, we observed that malaria drives Th1 cytokine responses, and accordingly, the less-functional Th1-polarized Tfh subset was preferentially activated and its activation did not correlate with antibody responses. These data provide insights into the Tfh cell biology underlying suboptimal antibody responses to malaria in children and suggest that vaccine strategies that promote CXCR3(-) Tfh cell responses may improve malaria vaccine efficacy.

SUBMITTER: Obeng-Adjei N

PROVIDER: S-EPMC4607674 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Publications

Circulating Th1-Cell-type Tfh Cells that Exhibit Impaired B Cell Help Are Preferentially Activated during Acute Malaria in Children.

Obeng-Adjei Nyamekye N Portugal Silvia S Tran Tuan M TM Yazew Takele B TB Skinner Jeff J Li Shanping S Jain Aarti A Felgner Philip L PL Doumbo Ogobara K OK Kayentao Kassoum K Ongoiba Aissata A Traore Boubacar B Crompton Peter D PD

Cell reports 20151001 2

Malaria-specific antibody responses are short lived in children, leaving them susceptible to repeated bouts of febrile malaria. The cellular and molecular mechanisms underlying this apparent immune deficiency are poorly understood. Recently, T follicular helper (Tfh) cells have been shown to play a critical role in generating long-lived antibody responses. We show that Malian children have resting PD-1(+)CXCR5(+)CD4(+) Tfh cells in circulation that resemble germinal center Tfh cells phenotypical ...[more]

PMID: 26440897

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Project description:During pregnancy, various immune effectors and molecules participating in the immune-microenvironment establish specific maternal tolerance toward the semi-allogeneic fetus. Activated maternal immune effectors by the trophoblast antigens, such as T helper (Th), T cytotoxic (Tc), T regulatory (Treg), and B cells, are involved in the regulation of adaptive immunity. Recognition of active signal through the T cell receptors stimulate the differentiation of naive CD3+CD4+ T cells into specific T cell subsets, such as Th1, Th2, Th9, Th17, Th22, and follicular Th cells (Tfh). Each of these subsets has a significant and distinct role in human pregnancy. Th1 immunity, characterized by immune-inflammatory responses, becomes dominant during the peri-implantation period, and the "controlled" Th1 immunity benefits the invading trophoblasts rather than harm. Quickly after the placental implantation, the early inflammatory Th1 immunity is shifted to the Th2 anti-inflammatory immune responses. The predominant Th2 immunity, which overrules the Th1 immunity at the placental implantation site, protects a fetus by balancing Th1 immunity and accommodate fetal and placental development. Moreover, Treg and Th9 cells regulate local inflammatory immune responses, potentially detrimental to the fetus. Th17 cells induce protective immunity against extracellular microbes during pregnancy. However, excessive Th17 immunity may induce uncontrolled neutrophil infiltration at the maternal-fetal interface. Other Th cell subsets such as Tfh cells, also contribute to pregnancy by setting up favorable humoral immunity during pregnancy. However, dysregulation of Th cell immunity during pregnancy may result in obstetrical complications, such as recurrent pregnancy losses (RPL) and preeclampsia (PE). With this review, we intend to deliver a comprehensive overview of CD4+ Th cell subsets, including Th1, Th2, Th9, Th17, Th22, and Tfh cells, in human pregnancy by reviewing their roles in normal and pathological pregnancies.

Dataset Information

Circulating Th1-Cell-type Tfh Cells that Exhibit Impaired B Cell Help Are Preferentially Activated during Acute Malaria in Children.

Publications

Circulating Th1-Cell-type Tfh Cells that Exhibit Impaired B Cell Help Are Preferentially Activated during Acute Malaria in Children.

Similar Datasets

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