Lymph-Node-Based CD3+ CD20+ Cells Emerge from Membrane Exchange between T Follicular Helper Cells and B Cells and Increase Their Frequency following Simian Immunodeficiency Virus Infection

• Authors: Sadia Samer, Emory University; Ankita Chowdhury, Emory University; Tomas Raul Wiche Salinas, Emory University; Perla M. Del Rio Estrada, Centro de Investigacion en Enfermedades Infecciosas; Morgan Reuter, University of Pennsylvania; Gregory K. Tharp, Emory University; Steven Bosinger, Emory University; Barbara Cervasi, Emory University; James Auger, Emory University; Kiran Gill, Emory University; Yuria Ablaneda-Terrazas, Centro Médico ABC Santa Fe; Gustavo Reyes-Teran, omisión Coordinadora de los Institutos Nacionales de Salud y Hospitales de Alta Especialidad; Jacob D. Estes, Leidos Biomedical Research; Michael R. Betts, University of Pennsylvania; Guido Silvestri, Emory University; Mirko Paiardini, Emory University
• Journal Title: Journal of Virology
• Volume: Volume 97, Number 6
• Publisher: American Society for Microbiology | 2023-05-23, Pages e01760-22
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1128/jvi.01760-22
• Subjects: Health Sciences, Immunology; Biology, Cell
• Keywords: CD3+ CD20+ cells; TFH; HIV infection; SIV infection; nonhuman primates; lymphoid tissues

Abstract

CD4+ T follicular helper (TFH) cells are key targets for human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) replication and contribute to the virus reservoir under antiretroviral therapy (ART). Here, we describe a novel CD3+ CD20+ double-positive (DP) lymphocyte subset, resident in secondary lymphoid organs of humans and rhesus macaques (RMs), that appear predominantly after membrane exchange between TFH and B cells. DP lymphocytes are enriched in cells displaying a TFH phenotype (CD4+ PD1hi CXCR5hi), function (interleukin 21 positive [IL-21+]), and gene expression profile. Importantly, expression of CD40L upon brief in vitro mitogen stimulation identifies, by specific gene-expression signatures, DP cells of TFH-cell origin versus those of B-cell origin. Analysis of 56 RMs showed that DP cells (i) significantly increase following SIV infection, (ii) are reduced after 12 months of ART in comparison to pre-ART levels, and (iii) expand to a significantly higher frequency following ART interruption. Quantification of total SIV-gag DNA on sorted DP cells from chronically infected RMs showed that these cells are susceptible to SIV infection. These data reinforce earlier observations that CD20+ T cells are infected and expanded by HIV infection, while suggesting that these cells phenotypically overlap activated CD4+ TFH cells that acquire CD20 expression via trogocytosis and can be targeted as part of therapeutic strategies aimed at HIV remission.