TY - JOUR
T1 - Identification and characterization of HIV-specific resident memory CD8+ T cells in human lymphoid tissue
AU - Buggert, Marcus
AU - Nguyen, Son
AU - de Oca, Gonzalo Salgado Montes
AU - Bengsch, Bertram
AU - Darko, Samuel
AU - Ransier, Amy
AU - Roberts, Emily R.
AU - del Alcazar, Daniel
AU - Brody, Irene Bukh
AU - Vella, Laura A.
AU - Beura, Lalit
AU - Wijeyesinghe, Sathi
AU - Herati, Ramin S.
AU - Del Rio Estrada, Perla M.
AU - Ablanedo-Terrazas, Yuria
AU - Kuri-Cervantes, Leticia
AU - Japp, Alberto Sada
AU - Manne, Sasikanth
AU - Vartanian, Shant
AU - Huffman, Austin
AU - Sandberg, Johan K.
AU - Gostick, Emma
AU - Nadolski, Gregory
AU - Silvestri, Guido
AU - Canaday, David H.
AU - Price, David A.
AU - Petrovas, Constantinos
AU - Su, Laura F.
AU - Vahedi, Golnaz
AU - Dori, Yoav
AU - Frank, Ian
AU - Itkin, Maxim G.
AU - John Wherry, E.
AU - Deeks, Steven G.
AU - Naji, Ali
AU - Reyes-Terán, Gustavo
AU - Masopust, David
AU - Douek, Daniel C.
AU - Betts, Michael R.
N1 - Publisher Copyright:
Copyright © 2018 The Authors, some rights reserved.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
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U2 - 10.1126/sciimmunol.aar4526
DO - 10.1126/sciimmunol.aar4526
M3 - Article
C2 - 29858286
AN - SCOPUS:85053482948
SN - 2470-9468
VL - 3
JO - Science Immunology
JF - Science Immunology
IS - 24
M1 - eaar4526
ER -