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

Autor: Marcus Buggert, Son Nguyen, Laura M McLane, Maria Steblyanko, Nadia Anikeeva, Dominic Paquin-Proulx, Perla M Del Rio Estrada, Yuria Ablanedo-Terrazas, Kajsa Noyan, Morgan A Reuter, Korey Demers, Johan K Sandberg, Michael A Eller, Hendrik Streeck, Marianne Jansson, Piotr Nowak, Anders Sönnerborg, David H Canaday, Ali Naji, E John Wherry, Merlin L Robb, Steven G Deeks, Gustavo Reyes-Teran, Yuri Sykulev, Annika C Karlsson, Michael R Betts
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: PLoS Pathogens, Vol 14, Iss 4, p e1006973 (2018)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1006973
Popis: 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.
Databáze: Directory of Open Access Journals
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