Authors

Marcus Buggert, University of Pennsylvania; Karolinska Institutet
Son Nguyen, University of Pennsylvania
Laura M. McLane, University of Pennsylvania
Maria Steblyanko, Thomas Jefferson University
Nadia Anikeeva, Thomas Jefferson University
Dominic Paquin-Proulx, Karolinska Institutet; Walter Reed Army Institute of Research; Henry M. Jackson Foundation for the Advancement of Military Medicine
Perla M Del Rio Estrada, Instituto Nacional de Enfermedades Respiratorias City
Yuria Ablanedo-Terrazas, Instituto Nacional de Enfermedades Respiratorias City
Kajsa Noyan, Karolinska Institutet
Morgan A. Reuter, University of Pennsylvania
Korey Demers, University of Pennsylvania
Johan K. Sandberg, Karolinska Institutet
Michael A. Eller, Walter Reed Army Institute of Research; Henry M. Jackson Foundation for the Advancement of Military Medicine
Hendrik Streeck, Walter Reed Army Institute of Research; Henry M. Jackson Foundation for the Advancement of Military Medicine; University Duisburg-Essen
Marianne Jansson, Lund University; Karolinska Institutet
Piotr Nowak, Karolinska Institutet
Anders Sönnerborg, Karolinska Institutet
David H. Canaday, Case Western Reserve University; Louis Stokes VA Medical Center
Ali Naji, University of Pennsylvania
E. John Wherry, University of Pennsylvania
Merlin L. Robb, Walter Reed Army Institute of Research; Henry M. Jackson Foundation for the Advancement of Military Medicine
Steven G Deeks, University of California; San Francisco General Hospital
Gustavo Reyes-Teran, Instituto Nacional de Enfermedades Respiratorias City
Yuri Sykulev, Thomas Jefferson UniversityFollow
Annika C. Karlsson, Karolinska Institutet
Michael R. Betts, University of Pennsylvania

Document Type

Article

Publication Date

4-1-2018

Comments

This article has been peer reviewed. It is the author’s final published version in PLoS Pathogens, Volume 14, Issue 4, April 2018, Article number e1006973.

The published version is available at https://doi.org/10.1371/journal.ppat.1006973. Copyright © Buggert et al.

Abstract

CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether effector CD4+ T cells expressing cytolytic molecules and β-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of β-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and eomesodermin (Eomes). This effector population is predominately found in peripheral blood and is limited in LNs regardless of HIV infection or treatment status. As a result, CD4+ T cells generally lack effector functions in LNs, including cytolytic capacity and IFNγ and β-chemokine expression, even in HIV elite controllers and during acute/early HIV infection. While we do find the presence of degranulating CD4+ T cells in LNs, these cells do not bear functional or transcriptional effector T cell properties and are inherently poor to form stable immunological synapses compared to their peripheral blood counterparts. We demonstrate that CD4+ T cell cytolytic function, phenotype, and programming in the peripheral blood is dissociated from those characteristics found in lymphoid tissues. Together, these data challenge our current models based on blood and suggest spatially and temporally dissociated mechanisms of viral control in lymphoid tissues.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Public Domain Dedication 1.0 License.

Language

English

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