Functional Impairment of Central Memory CD4 T Cells Is a Potential Early Prognostic Marker for Changing Viral Load in SHIV-Infected Rhesus Macaques

Hong He,Guojun Yang,K Jagannadha Sastry,Stephanie Buchl,Bharti Nehete,Eric Wieder,Pramod N Nehete,Fu-Sheng Wang

doi:10.1371/journal.pone.0019607

Hong He, Guojun Yang + Show 6 more

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https://doi.org/10.1371/journal.pone.0019607

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Abstract

In HIV infection there is a paucity of literature about the degree of immune dysfunction to potentially correlate and/or predict disease progression relative to CD4+ T cells count or viral load. We assessed functional characteristics of memory T cells subsets as potential prognostic markers for changing viral loads and/or disease progression using the SHIV-infected rhesus macaque model. Relative to long-term non-progressors with low/undetectable viral loads, those with chronic plasma viremia, but clinically healthy, exhibited significantly lower numbers and functional impairment of CD4+ T cells, but not CD8+ T cells, in terms of IL-2 production by central memory subset in response to PMA and ionomycine (PMA+I) stimulation. Highly viremic animals showed impaired cytokine-production by all T cells subsets. These results suggest that functional impairment of CD4+ T cells in general, and of central memory subset in particular, may be a potential indicator/predictor of chronic infection with immune dysfunction, which could be assayed relatively easily using non-specific PMA+I stimulation.

Highlights

Human immunodeficiency virus (HIV) infection exerts profound effects on the immune system in terms of effectively evading the antiviral antibody responses as well as progressively compromising the functional abilities of the cellular immune responses that lead to the development of acquired immunodeficiency syndrome (AIDS) characterized by life-threatening opportunistic infections and malignancies [1,2]
Using flow cytometry to measure intracellular cytokines after stimulation of peripheral blood mononuclear cells (PBMC) with recombinant HIV proteins or overlapping peptide pools, HIV-specific CD4+ T cells were detected in individuals with active HIV-1 infection that declined with prolonged viral suppression [8]
We describe here multicolor flow cytometry analyses combining detailed phenotypic and functional characterization of total as well as memory subsets of CD4+ and CD8+ T cells from SHIV-infected rhesus macaques with no clinical symptoms but exhibiting markedly differing viral loads associated with differential cytokine production in response to non-specific in vitro stimulation with PMA and ionomycine (PMA+I)

Summary

Introduction

Human immunodeficiency virus (HIV) infection exerts profound effects on the immune system in terms of effectively evading the antiviral antibody responses as well as progressively compromising the functional abilities of the cellular immune responses that lead to the development of acquired immunodeficiency syndrome (AIDS) characterized by life-threatening opportunistic infections and malignancies [1,2]. We describe here multicolor flow cytometry analyses combining detailed phenotypic and functional characterization of total as well as memory subsets of CD4+ and CD8+ T cells from SHIV-infected rhesus macaques with no clinical symptoms but exhibiting markedly differing viral loads associated with differential cytokine production in response to non-specific in vitro stimulation with PMA+I.

Results

Conclusion