Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease.

Authors

• Marcus Buggert, University of Pennsylvania; Karolinska Institutet
• Son Nguyen, University of Pennsylvania
• Laura M. McLane, University of Pennsylvania
• Maria Steblyanko, Thomas Jefferson UniversityFollow
• Nadia Anikeeva, Thomas Jefferson UniversityFollow
• 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 PennsylvaniaFollow
• 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.

Recommended Citation

Buggert, Marcus; Nguyen, Son; McLane, Laura M.; Steblyanko, Maria; Anikeeva, Nadia; Paquin-Proulx, Dominic; Del Rio Estrada, Perla M; Ablanedo-Terrazas, Yuria; Noyan, Kajsa; Reuter, Morgan A.; Demers, Korey; Sandberg, Johan K.; Eller, Michael A.; Streeck, Hendrik; Jansson, Marianne; Nowak, Piotr; Sönnerborg, Anders; Canaday, David H.; Naji, Ali; Wherry, E. John; Robb, Merlin L.; Deeks, Steven G; Reyes-Teran, Gustavo; Sykulev, Yuri; Karlsson, Annika C.; and Betts, Michael R., "Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease." (2018). Department of Medical Oncology Faculty Papers. Paper 80.
https://jdc.jefferson.edu/medoncfp/80

Creative Commons License

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

PubMed ID

29652923

Language

English