Predicting the impact of CD8+ T cell polyfunctionality on HIV disease progression

Graw F, Regoes RR (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Journal of Virology American Society for Microbiology

Book Volume: 88

Pages Range: 10134-10145

Journal Issue: 17

DOI: 10.1128/JVI.00647-14

Abstract

During the chronic phase of HIV-1 infection, polyfunctional CD8+ T cell responses, which are characterized by a high frequency of cells able to secrete multiple cytokines simultaneously, are associated with lower virus loads and slower disease progression. This relationship may arise for different reasons. Polyfunctional responses may simply be stronger. Alternatively, it could be that the increased functional diversity in polyfunctional responses leads to lower virus loads and slower disease progression. Lastly, polyfunctional responses could contain more CD8+ T cells that mediate a specific key function that is primarily responsible for viral control. Disentangling the influences of overall strength, functional diversity, and specific function on viral control and disease progression is very relevant for the rational design of vaccines and immunotherapy using cellular immune responses. We developed a mathematical model to study how polyfunctional CD8+ T cell responses mediating lytic and nonlytic effector functions affect the CD4+ T cell count and plasma viral load. We based our model on in vitro data on the efficacy of gamma interferon (IFN-γ) and macrophage inflammatory protein 1β (MIP-1β)/RANTES against HIV. We find that the strength of the response is a good predictor of disease progression, while functional diversity has only a minor influence. In addition, our model predicts for realistic levels of cytotoxicity that immune responses dominated by nonlytic effector functions most positively influence disease outcome.

Authors with CRIS profile

Frederik Graw

Involved external institutions

Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich CH Switzerland (CH)

How to cite

APA:

Graw, F., & Regoes, R.R. (2014). Predicting the impact of CD8+ T cell polyfunctionality on HIV disease progression. Journal of Virology, 88(17), 10134-10145. https://doi.org/10.1128/JVI.00647-14

MLA:

Graw, Frederik, and Roland R. Regoes. "Predicting the impact of CD8+ T cell polyfunctionality on HIV disease progression." Journal of Virology 88.17 (2014): 10134-10145.

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