Identification and characterization of HIV-specific resident memory CD8+ T cells in human lymphoid tissue

Marcus Buggert, Son Nguyen, Gonzalo Salgado Montes de Oca, Bertram Bengsch, Samuel Darko, Amy Ransier, Emily R. Roberts, Daniel del Alcazar, Irene Bukh Brody, Laura A. Vella, Lalit Beura, Sathi Wijeyesinghe, Ramin S. Herati, Perla M. Del Rio Estrada, Yuria Ablanedo-Terrazas, Leticia Kuri-Cervantes, Alberto Sada Japp, Sasikanth Manne, Shant Vartanian, Austin HuffmanJohan K. Sandberg, Emma Gostick, Gregory Nadolski, Guido Silvestri, David H. Canaday, David A. Price, Constantinos Petrovas, Laura F. Su, Golnaz Vahedi, Yoav Dori, Ian Frank, Maxim G. Itkin, E. John Wherry, Steven G. Deeks, Ali Naji, Gustavo Reyes-Terán, David Masopust, Daniel C. Douek, Michael R. Betts

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

Current paradigms of CD8+ T cell–mediated protection in HIV infection center almost exclusively on studies of peripheral blood, which is thought to provide a window into immune activity at the predominant sites of viral replication in lymphoid tissues (LTs). Through extensive comparison of blood, thoracic duct lymph (TDL), and LTs in different species, we show that many LT memory CD8+ T cells bear phenotypic, transcriptional, and epigenetic signatures of resident memory T cells (TRMs). Unlike their circulating counterparts in blood or TDL, most of the total and follicular HIV-specific CD8+ T cells in LTs also resemble TRMs. Moreover, high frequencies of HIV-specific CD8+ TRMs with skewed clonotypic profiles relative to matched blood samples are present in LTs of individuals who spontaneously control HIV replication in the absence of antiretroviral therapy (elite controllers). Single-cell RNA sequencing analysis confirmed that HIV-specific TRMs are enriched for effector-related immune genes and signatures compared with HIV-specific non-TRMs in elite controllers. Together, these data indicate that previous studies in blood have largely failed to capture the major component of HIV-specific CD8+ T cell responses resident within LTs.

Original languageEnglish (US)
Article numbereaar4526
JournalScience Immunology
Volume3
Issue number24
DOIs
StatePublished - 2018

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Copyright © 2018 The Authors, some rights reserved.

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