Journal article
Memory CD4 T cells that co-express PD1 and CTLA4 have reduced response to activating stimuli facilitating HIV latency
TA Rasmussen, JM Zerbato, A Rhodes, C Tumpach, A Dantanarayana, JH McMahon, JSY Lau, JJ Chang, C Gubser, W Brown, R Hoh, M Krone, R Pascoe, CY Chiu, M Bramhall, HJ Lee, A Haque, R Fromentin, N Chomont, J Milush Show all
Cell Reports Medicine | Published : 2022
Abstract
Programmed cell death 1 (PD1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4) suppress CD4+ T cell activation and may promote latent HIV infection. By performing leukapheresis (n = 21) and lymph node biopsies (n = 8) in people with HIV on antiretroviral therapy (ART) and sorting memory CD4+ T cells into subsets based on PD1/CTLA4 expression, we investigate the role of PD1 and CTLA 4 in HIV persistence. We show that double-positive (PD1+CTLA4+) cells in blood contain more HIV DNA compared with double-negative (PD1−CTLA4−) cells but still have a lower proportion of cells producing multiply spliced HIV RNA after stimulation as well as reduced upregulation of T cell activation and prolif..
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Awarded by Merck
Funding Acknowledgements
We acknowledge Tina Luke, Angela Hind, Catherine Li, and Lankesha Yapa from the Melbourne Cytometry Platform at the Doherty Institute for Infection and Immunity for assistance with flow cytometry and cell sorting. We also acknowledge Socheata Chea and Surekha Tennakoon for assistance with laboratory procedures. This work was kindly supported by the Harold and Cora Brennen Trust through purchase of the 10X Chromium Controller. The study was funded by a grant from American Foundation for AIDS Research (amfAR; 109226-58-RGRL) and the National Institutes of Health Delaney AIDS Research Enterprise (DARE) Collaboratory (UM1AI126611), The National Health and Medical Research Council (NHMRC; GNT1149990) of Australia. We thank all study participants for donating their time and samples to contribute to the study. A huge thanks goes to Michelle Hagenauer and the clinical research unit at The Department of Infectious Diseases at Alfred Hospital and Marian Kerbleski and the SCOPE team at UCSF for help with identifying study participants and coordinating sample collection and study visits.