Th1-like Plasmodium -Specific Memory CD4 + T Cells Support Humoral Immunity

Zander, Ryan; Vijay, Rahul; Pack, Angela D.; Guthmiller, Jenna J.; Graham, Antonnette V.; Lindner, Scott E.; Vaughan, Ashley M.; Kappe, Stefan H. I.; Butler, Noah S.

doi:10.1016/j.celrep.2017.10.077

Cited by 54 publications

(44 citation statements)

References 79 publications

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“…How then are MHC-II-restricted NK1.1 + CD4 + T cells categorized amongst conventional CD4 + T cells and NK-T cells? Our findings indicate that NK1.1 + and NK1.1 − CD4 + T cells are composed of a heterogeneous population of cells expressing markers associated with Th1 and Tfh cells, similar to what has been reported by others ( 21 , 23 , 33 – 35 ), further supporting the idea that T cells transition through an intermediate state prior to full commitment toward Th1 or Tfh cell differentiation ( 35 ). Perhaps, NK1.1 expression defines one of these intermediate states.…”

Section: Discussionsupporting

confidence: 90%

NK1.1 Expression Defines a Population of CD4+ Effector T Cells Displaying Th1 and Tfh Cell Properties That Support Early Antibody Production During Plasmodium yoelii Infection

et al. 2018

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Early plasmablast induction is a hallmark of Plasmodium infection and is thought to contribute to the control of acute parasite burden. Although long understood to be a T-cell dependent phenomenon, regulation of early plasmablast differentiation, however, is poorly understood. Here, we identify a population of CD4+ T cells that express the innate NK cell marker NK1.1 as an important source of T cell help for early plasmablast and parasite-specific Ab production. Interestingly, NK1.1+ CD4+ T cells arise from conventional, naive NK1.1− CD4+ T cells, and their generation is independent of CD1d but critically reliant on MHC-II. CD4+ T cells that express NK1.1 early after activation produce IFN-γ and IL-21, and express the follicular helper T (Tfh) cell markers ICOS, PD-1 and CXCR5 more frequently than NK1.1− CD4+ T cells. Further analysis of this population revealed that NK1.1+ Tfh-like cells were more regularly complexed with plasmablasts than NK1.1− Tfh-like cells. Ultimately, depletion of NK1.1+ cells impaired class-switched parasite-specific antibody production during early Plasmodium yoelii infection. Together, these data suggest that expression of NK1.1 defines a population of rapidly expanding effector CD4+ T cells that specifically promote plasmablast induction during Plasmodium infection and represent a subset of T cells whose modulation could promote effective vaccine design.

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Section: Discussionsupporting

confidence: 90%

NK1.1 Expression Defines a Population of CD4+ Effector T Cells Displaying Th1 and Tfh Cell Properties That Support Early Antibody Production During Plasmodium yoelii Infection

et al. 2018

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“…CD49d to examine differences in antigen-experienced CD4 + T cells between WT and Icos -/mice. This approach has been confirmed for viral infection [33] and other models of rodent malaria [34][35][36]. In the absence of CQ, there was a similar percentage and number of CD49d + CD11a + CD4 + T cells in the spleen of WT and Icos -/mice (S1 Fig).…”

Section: Plos Pathogensmentioning

confidence: 61%

ICOS signaling promotes a secondary humoral response after re-challenge with Plasmodium chabaudi chabaudi AS

2020

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The co-stimulatory molecule ICOS is associated with the induction and regulation of T helper cell responses, including the differentiation of follicular helper T (Tfh) cells and the formation and maintenance of memory T cells. However, the role of ICOS signaling in secondary immune responses is largely unexplored. Here we show that memory T cell formation and maintenance are influenced by persistent infection with P. chabaudi chabaudi AS infection, as memory T cell numbers decline in wild-type and Icos-/mice after drug-clearance. Following drug-clearance Icos-/mice display a relapsing parasitemia that occurs more frequently and with higher peaks compared to wild-type mice after re-challenge. The secondary immune response in Icos-/mice is characterized by significant impairment in the expansion of effector cells with a Tfh-like phenotype, which is associated with a diminished and delayed parasite-specific Ab response and the absence of germinal centers. Similarly, the administration of an anti-ICOSL antagonizing antibody to wild-type mice before and after reinfection with P. c. chabaudi AS leads to an early defect in Tfh cell expansion and parasite-specific antibody production, confirming a need for ICOS-ICOSL interactions to promote memory B cell responses. Furthermore, adoptive transfer of central memory T (T CM) cells from wild-type and Icos-/mice into tcrb-/mice to directly evaluate the ability of T CM cells to give rise to Tfh cells revealed that T CM cells from wild-type mice acquire a mixed Th1-and Tfh-like phenotype after P. c. chabaudi AS infection. While T CM cells from Icos-/mice expand and display markers of activation to a similar degree as their WT counterparts, they displayed a reduced capacity to upregulate markers indicative of a Tfh cell phenotype, resulting in a diminished humoral response. Together these findings verify that ICOS signaling in memory T cells plays an integral role in promoting T cell effector responses during secondary infection with P. c. chabaudi AS.

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“…However, it is likely that TLRs might play an important role in the innate immune response to SARS-CoV-2 infection 42 . Though, we did not use any adjuvants, it is reported that TLRs (TLR3 and TLR4) can effectively bind with spike protein of the CoV 43 . The molecular docking analysis of the CoV-RMEN through HADDOCK showed that the chimeric protein can establish stable protein-protein interactions with TLRs (TLR-3,TLR-4) 41 indicating efficient activation of these surface molecules which is very crucial for immune activation of dendritic cells for subsequent antigen processing and presentation to CD4+ and CD8+ T-cells via MHC-II and MHC-1, respectively corroborating the findings of different earlier studies 11, 20, 21 .…”

Section: Discussionmentioning

confidence: 99%

Epitope-based chimeric peptide vaccine design against S, M and E proteins of SARS-CoV-2 etiologic agent of global pandemic COVID-19: anin silicoapproach

Rahman

Hoque

Islam

et al. 2020

Preprint

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Th1-like Plasmodium -Specific Memory CD4 + T Cells Support Humoral Immunity

Cited by 54 publications

References 79 publications

NK1.1 Expression Defines a Population of CD4+ Effector T Cells Displaying Th1 and Tfh Cell Properties That Support Early Antibody Production During Plasmodium yoelii Infection

NK1.1 Expression Defines a Population of CD4+ Effector T Cells Displaying Th1 and Tfh Cell Properties That Support Early Antibody Production During Plasmodium yoelii Infection

ICOS signaling promotes a secondary humoral response after re-challenge with Plasmodium chabaudi chabaudi AS

Epitope-based chimeric peptide vaccine design against S, M and E proteins of SARS-CoV-2 etiologic agent of global pandemic COVID-19: anin silicoapproach

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