Impaired CD4 T cell memory response to Streptococcus pneumoniae precedes CD4 T cell depletion in HIV-infected Malawian adults

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dc.contributor.authorGlennie, Sarah Jen_ZA
dc.contributor.authorSepako, Enochen_ZA
dc.contributor.authorMzinza, Daviden_ZA
dc.contributor.authorHarawa, Visopoen_ZA
dc.contributor.authorMiles, David J Cen_ZA
dc.contributor.authorJambo, Kondwani Cen_ZA
dc.contributor.authorGordon, Stephen Ben_ZA
dc.contributor.authorWilliams, Neil Aen_ZA
dc.contributor.authorHeyderman, Robert Sen_ZA
dc.date.accessioned2016-01-11T06:52:15Z
dc.date.available2016-01-11T06:52:15Z
dc.date.issued2011en_ZA
dc.description.abstractObjective Invasive pneumococcal disease (IPD) is a leading cause of morbidity and mortality in HIV-infected African adults. CD4 T cell depletion may partially explain this high disease burden but those with relatively preserved T cell numbers are still at increased risk of IPD. This study evaluated the extent of pneumococcal-specific T cell memory dysfunction in asymptomatic HIV infection early on in the evolution of the disease. METHODS: Peripheral blood mononuclear cells were isolated from asymptomatic HIV-infected and HIV-uninfected Malawian adults and stained to characterize the underlying degree of CD4 T cell immune activation, senescence and regulation. Pneumococcal-specific T cell proliferation, IFN-γ, IL-17 production and CD154 expression was assessed using flow cytometry and ELISpot. RESULTS: We find that in asymptomatic HIV-infected Malawian adults, there is considerable immune disruption with an increase in activated and senescent CD4 + CD38 + PD-1 + and CD4 + CD25 high Foxp3 + Treg cells. In the context of high pneumococcal exposure and therefore immune stimulation, show a failure in pneumococcal-specific memory T cell proliferation, skewing of T cell cytokine production with preservation of interleukin-17 but decreased interferon-gamma responses, and failure of activated T cells to express the co-stimulatory molecule CD154. CONCLUSION: Asymptomatic HIV-infected Malawian adults show early signs of pneumococcal- specific immune dysregulation with a shift in the balance of CD4 memory, T helper 17 cells and Treg. Together these data offer a mechanistic understanding of how antigen-specific T cell dysfunction occurs prior to T cell depletion and may explain the early susceptibility to IPD in those with relatively preserved CD4 T cell numbers.en_ZA
dc.identifier.apacitationGlennie, S. J., Sepako, E., Mzinza, D., Harawa, V., Miles, D. J. C., Jambo, K. C., ... Heyderman, R. S. (2011). Impaired CD4 T cell memory response to Streptococcus pneumoniae precedes CD4 T cell depletion in HIV-infected Malawian adults. <i>PLoS One</i>, http://hdl.handle.net/11427/16261en_ZA
dc.identifier.chicagocitationGlennie, Sarah J, Enoch Sepako, David Mzinza, Visopo Harawa, David J C Miles, Kondwani C Jambo, Stephen B Gordon, Neil A Williams, and Robert S Heyderman "Impaired CD4 T cell memory response to Streptococcus pneumoniae precedes CD4 T cell depletion in HIV-infected Malawian adults." <i>PLoS One</i> (2011) http://hdl.handle.net/11427/16261en_ZA
dc.identifier.citationGlennie, S. J., Sepako, E., Mzinza, D., Harawa, V., Miles, D. J., Jambo, K. C., ... & Heyderman, R. S. (2011). Impaired CD4 T cell memory response to Streptococcus pneumoniae precedes CD4 T cell depletion in HIV-infected Malawian adults. PloS one, 6(9), e25610. doi:10.1371/journal.pone.0025610en_ZA
dc.identifier.ris TY - Journal Article AU - Glennie, Sarah J AU - Sepako, Enoch AU - Mzinza, David AU - Harawa, Visopo AU - Miles, David J C AU - Jambo, Kondwani C AU - Gordon, Stephen B AU - Williams, Neil A AU - Heyderman, Robert S AB - Objective Invasive pneumococcal disease (IPD) is a leading cause of morbidity and mortality in HIV-infected African adults. CD4 T cell depletion may partially explain this high disease burden but those with relatively preserved T cell numbers are still at increased risk of IPD. This study evaluated the extent of pneumococcal-specific T cell memory dysfunction in asymptomatic HIV infection early on in the evolution of the disease. METHODS: Peripheral blood mononuclear cells were isolated from asymptomatic HIV-infected and HIV-uninfected Malawian adults and stained to characterize the underlying degree of CD4 T cell immune activation, senescence and regulation. Pneumococcal-specific T cell proliferation, IFN-γ, IL-17 production and CD154 expression was assessed using flow cytometry and ELISpot. RESULTS: We find that in asymptomatic HIV-infected Malawian adults, there is considerable immune disruption with an increase in activated and senescent CD4 + CD38 + PD-1 + and CD4 + CD25 high Foxp3 + Treg cells. In the context of high pneumococcal exposure and therefore immune stimulation, show a failure in pneumococcal-specific memory T cell proliferation, skewing of T cell cytokine production with preservation of interleukin-17 but decreased interferon-gamma responses, and failure of activated T cells to express the co-stimulatory molecule CD154. CONCLUSION: Asymptomatic HIV-infected Malawian adults show early signs of pneumococcal- specific immune dysregulation with a shift in the balance of CD4 memory, T helper 17 cells and Treg. Together these data offer a mechanistic understanding of how antigen-specific T cell dysfunction occurs prior to T cell depletion and may explain the early susceptibility to IPD in those with relatively preserved CD4 T cell numbers. DA - 2011 DB - OpenUCT DO - 10.1371/journal.pone.0025610 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2011 T1 - Impaired CD4 T cell memory response to Streptococcus pneumoniae precedes CD4 T cell depletion in HIV-infected Malawian adults TI - Impaired CD4 T cell memory response to Streptococcus pneumoniae precedes CD4 T cell depletion in HIV-infected Malawian adults UR - http://hdl.handle.net/11427/16261 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16261
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0025610
dc.identifier.vancouvercitationGlennie SJ, Sepako E, Mzinza D, Harawa V, Miles DJC, Jambo KC, et al. Impaired CD4 T cell memory response to Streptococcus pneumoniae precedes CD4 T cell depletion in HIV-infected Malawian adults. PLoS One. 2011; http://hdl.handle.net/11427/16261.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentSouth African Tuberculosis Vaccine Initiative (SATVI)en_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2011 Glennie et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherHIV infectionsen_ZA
dc.subject.otherT helper cellsen_ZA
dc.subject.otherFlow cytometryen_ZA
dc.subject.otherMemory T cellsen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherAdultsen_ZA
dc.subject.otherInfectious disease controlen_ZA
dc.titleImpaired CD4 T cell memory response to Streptococcus pneumoniae precedes CD4 T cell depletion in HIV-infected Malawian adultsen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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