Long-term Maintenance of CD4 T Cell Memory Responses to Malaria Antigens in Malian Children Coinfected with Schistosoma haematobium

Polyparasitism is common in the developing world. We have previously demonstrated that schistosomiasis-positive (SP) Malian children, aged 4–8 years, are protected from malaria compared to matched schistosomiasis-negative (SN) children. The effect of concomitant schistosomiasis upon acquisition of T...

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Main Authors: Kirsten E. Lyke, Abdoulaye Dabo, Charles Arama, Issa Diarra, Christopher V. Plowe, Ogobara K. Doumbo, Marcelo B. Sztein
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-02-01
Series:Frontiers in Immunology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fimmu.2017.01995/full
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author Kirsten E. Lyke
Kirsten E. Lyke
Abdoulaye Dabo
Charles Arama
Issa Diarra
Christopher V. Plowe
Christopher V. Plowe
Ogobara K. Doumbo
Marcelo B. Sztein
author_facet Kirsten E. Lyke
Kirsten E. Lyke
Abdoulaye Dabo
Charles Arama
Issa Diarra
Christopher V. Plowe
Christopher V. Plowe
Ogobara K. Doumbo
Marcelo B. Sztein
author_sort Kirsten E. Lyke
collection DOAJ
description Polyparasitism is common in the developing world. We have previously demonstrated that schistosomiasis-positive (SP) Malian children, aged 4–8 years, are protected from malaria compared to matched schistosomiasis-negative (SN) children. The effect of concomitant schistosomiasis upon acquisition of T cell memory is unknown. We examined antigen-specific T cell frequencies in 48 Malian children aged 4–14 to a pool of malaria blood stage antigens, and a pool of schistosomal antigens, at a time point during a malaria episode and at a convalescent time point ~6 months later, following cessation of malaria transmission. CD4+ T cell-derived memory responses, defined as one or more significant cytokine (IFN-γ, TNF-α, IL-2, and/or IL-17A) responses, was measured to schistoma antigens in 18/23 SP children at one or both time points, compared to 4/23 SN children (P < 0.0001). At the time of malaria infection, 12/24 SN children and 15/23 SP children (P = 0.29) stimulated with malaria antigens demonstrated memory recall as defined by CD4-derived cytokine production. This compares to 7/23 SN children and 16/23 SP children (P = 0.009) at the convalescent timepoint. 46.2% of cytokine-producing CD4+ T cells expressed a single cytokine after stimulation with malaria antigen during the malaria episode. This fell to 40.9% at follow-up with a compensatory rise of multifunctional cytokine secretion over time, a phenomenon consistent with memory maturation. The majority (53.2–59.5%) of responses derived from CD45RA−CD62L− effector memory T cells with little variation in the phenotype depending upon the time point or the study cohort. We conclude that detectable T cell memory responses can be measured against both malaria and schistosoma antigens and that the presence of Schistosoma haematobium may be associated with long-term maintenance of T memory to malaria.
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spelling doaj.art-a42457d4d5164e7aac555bae71c91f9b2022-12-21T22:52:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-02-01810.3389/fimmu.2017.01995323622Long-term Maintenance of CD4 T Cell Memory Responses to Malaria Antigens in Malian Children Coinfected with Schistosoma haematobiumKirsten E. Lyke0Kirsten E. Lyke1Abdoulaye Dabo2Charles Arama3Issa Diarra4Christopher V. Plowe5Christopher V. Plowe6Ogobara K. Doumbo7Marcelo B. Sztein8Center for Vaccine Development, Institute for Global Health, School of Medicine, University of Maryland, Baltimore, MD, United StatesDivision of Malaria Research, Institute for Global Health, School of Medicine, University of Maryland, Baltimore, MD, United StatesMalaria Research and Training Center, International Centers for Excellence in Research (NIH), University of Science Techniques and Technologies of Bamako, Bamako, MaliMalaria Research and Training Center, International Centers for Excellence in Research (NIH), University of Science Techniques and Technologies of Bamako, Bamako, MaliMalaria Research and Training Center, International Centers for Excellence in Research (NIH), University of Science Techniques and Technologies of Bamako, Bamako, MaliCenter for Vaccine Development, Institute for Global Health, School of Medicine, University of Maryland, Baltimore, MD, United StatesDivision of Malaria Research, Institute for Global Health, School of Medicine, University of Maryland, Baltimore, MD, United StatesMalaria Research and Training Center, International Centers for Excellence in Research (NIH), University of Science Techniques and Technologies of Bamako, Bamako, MaliCenter for Vaccine Development, Institute for Global Health, School of Medicine, University of Maryland, Baltimore, MD, United StatesPolyparasitism is common in the developing world. We have previously demonstrated that schistosomiasis-positive (SP) Malian children, aged 4–8 years, are protected from malaria compared to matched schistosomiasis-negative (SN) children. The effect of concomitant schistosomiasis upon acquisition of T cell memory is unknown. We examined antigen-specific T cell frequencies in 48 Malian children aged 4–14 to a pool of malaria blood stage antigens, and a pool of schistosomal antigens, at a time point during a malaria episode and at a convalescent time point ~6 months later, following cessation of malaria transmission. CD4+ T cell-derived memory responses, defined as one or more significant cytokine (IFN-γ, TNF-α, IL-2, and/or IL-17A) responses, was measured to schistoma antigens in 18/23 SP children at one or both time points, compared to 4/23 SN children (P < 0.0001). At the time of malaria infection, 12/24 SN children and 15/23 SP children (P = 0.29) stimulated with malaria antigens demonstrated memory recall as defined by CD4-derived cytokine production. This compares to 7/23 SN children and 16/23 SP children (P = 0.009) at the convalescent timepoint. 46.2% of cytokine-producing CD4+ T cells expressed a single cytokine after stimulation with malaria antigen during the malaria episode. This fell to 40.9% at follow-up with a compensatory rise of multifunctional cytokine secretion over time, a phenomenon consistent with memory maturation. The majority (53.2–59.5%) of responses derived from CD45RA−CD62L− effector memory T cells with little variation in the phenotype depending upon the time point or the study cohort. We conclude that detectable T cell memory responses can be measured against both malaria and schistosoma antigens and that the presence of Schistosoma haematobium may be associated with long-term maintenance of T memory to malaria.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01995/fullmalariaschistosomiasiscoinfectionmultifunctional T cellsT cell memorymemory
spellingShingle Kirsten E. Lyke
Kirsten E. Lyke
Abdoulaye Dabo
Charles Arama
Issa Diarra
Christopher V. Plowe
Christopher V. Plowe
Ogobara K. Doumbo
Marcelo B. Sztein
Long-term Maintenance of CD4 T Cell Memory Responses to Malaria Antigens in Malian Children Coinfected with Schistosoma haematobium
Frontiers in Immunology
malaria
schistosomiasis
coinfection
multifunctional T cells
T cell memory
memory
title Long-term Maintenance of CD4 T Cell Memory Responses to Malaria Antigens in Malian Children Coinfected with Schistosoma haematobium
title_full Long-term Maintenance of CD4 T Cell Memory Responses to Malaria Antigens in Malian Children Coinfected with Schistosoma haematobium
title_fullStr Long-term Maintenance of CD4 T Cell Memory Responses to Malaria Antigens in Malian Children Coinfected with Schistosoma haematobium
title_full_unstemmed Long-term Maintenance of CD4 T Cell Memory Responses to Malaria Antigens in Malian Children Coinfected with Schistosoma haematobium
title_short Long-term Maintenance of CD4 T Cell Memory Responses to Malaria Antigens in Malian Children Coinfected with Schistosoma haematobium
title_sort long term maintenance of cd4 t cell memory responses to malaria antigens in malian children coinfected with schistosoma haematobium
topic malaria
schistosomiasis
coinfection
multifunctional T cells
T cell memory
memory
url http://journal.frontiersin.org/article/10.3389/fimmu.2017.01995/full
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