Impaired CD4 T Cell Memory Response to Streptococcus pneumoniae Precedes CD4 T Cell Depletion in HIV-Infected Malawian Adults

Glennie, Sarah, Sepako, Enoch, Mzinza, David, Harawa, Visopo, Miles, David J.C., Jambo, Kondwani ORCID: https://orcid.org/0000-0002-3195-2210, Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116, Williams, Neil A and Heyderman, Robert (2011) 'Impaired CD4 T Cell Memory Response to Streptococcus pneumoniae Precedes CD4 T Cell Depletion in HIV-Infected Malawian Adults'. PLoS ONE, Vol 6, Issue 9, e25610.

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Abstract

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-c, 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+CD25highFoxp3+ 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.

Item Type:	Article
Subjects:	WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.5 Complications
Faculty: Department:	Groups (2002 - 2012) > Clinical Group
Digital Object Identifer (DOI):	https://doi.org/10.1371/journal.pone.0025610
Depositing User:	Users 43 not found.
Date Deposited:	08 Nov 2011 16:15
Last Modified:	07 Oct 2019 08:23
URI:	https://archive.lstmed.ac.uk/id/eprint/2395

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