Journal article
Activation of CXCR3+ Tfh cells and B cells in lymph nodes during acute HIV-1 infection correlates with HIV-specific antibody development
Journal of virology, v 99(3)
11 Feb 2025
PMID: 39932316
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Lymph node T follicular helper (Tfh) cells and germinal center (GC) B cells are critical to generate potent antibodies but are rarely possible to study in humans. To understand how Tfh/GC B-cell interactions during acute HIV-1 infection (AHI) impact the generation of HIV-specific antibodies, we performed a unique cross-sectional analysis of inguinal lymph node biopsies taken prior to antiretroviral therapy (ART) initiation in AHI. Although total Tfh and GC B cell frequencies did not change during AHI, increased frequencies of proliferating Th1-like CXCR3+ Tfh, CXCR3+ non-GC B cells, and total CXCR3+ GC B cells correlated with gp120-specific IgG antibody levels in AHI. Frequencies of proliferating CXCR3+ Tfh in AHI also correlated with gp120-specific IgG antibody levels after 48 weeks of ART, antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and increased antibody binding to infected cells after ART. Importantly, while beneficial for antibody development, CXCR3+ Tfh cells were also infected by HIV-1 at higher frequencies than their CXCR3− counterparts and may contribute to the initial dissemination of HIV-1 in follicles. Together, these data suggest that activation of CXCR3+ Tfh cells is associated with induction of the germinal center response and subsequent antibody development, making these cells an important target for future therapeutic interventions.IMPORTANCEEarly initiation of antiretroviral therapy (ART) is important to limit the seeding of the long-lasting HIV-1 reservoir; however, it also precludes the development of HIV-specific antibodies that can help control the virus if ART is stopped. Antibody development occurs within germinal centers in the lymph node and requires activation of both antigen-specific B cells and T follicular helper cells (Tfh), a specialized CD4+ cell that provides B cell help. To understand how early ART initiation may prohibit antibody development, we analyzed the frequencies and activation status of Tfh and B cells in lymph node biopsies collected in the different stages of acute HIV-1 infection. Our data suggest that decreased antibody development after early ART initiation may be due to limited germinal center development at the time of treatment and that new interventions that target activation of CXCR3+ Tfh may be beneficial to increase long-term HIV-specific antibody levels.
Metrics
Details
- Title
- Activation of CXCR3+ Tfh cells and B cells in lymph nodes during acute HIV-1 infection correlates with HIV-specific antibody development
- Creators
- Julie L. Mitchell - Oregon Health & Science UniversitySupranee Buranapraditkun - Chulalongkorn UniversityPierre Gantner - Centre Hospitalier de l’Université de MontréalHiroshi Takata - Oregon Health & Science UniversityKenneth Dietze - Henry M. Jackson FoundationKombo F. N'guessan - ,Justin Pollara - Duke Medical CenterJunsuke Nohara - Duke Medical CenterRoshell Muir - Drexel UniversityEugene Kroon - ,Suteeraporn Pinyakorn - Walter Reed Army Institute of ResearchNicha Tulmethakaan - ,Sopark Manasnayakorn - Chulalongkorn UniversitySuthat Chottanapund - ,Pattarawat Thantiworasit - Chulalongkorn UniversityPeeriya Prueksakaew - ,Nisakorn Ratnaratorn - ,Suwanna Puttamaswin - ,Bessara Nuntapinit - Armed Forces Research Institute of Medical ScienceLawrence Fox - National Institutes of HealthElias K. Haddad - Drexel UniversityDominic Paquin-Proulx - Henry M. Jackson FoundationPraphan Phanuphak - ,Carlo P. Sacdalan - Chulalongkorn UniversityNittaya Phanuphak - HIV Netherlands Australia Thailand Research CollaborationJintanat Ananworanich - Amsterdam University Medical CentersDenise Hsu - Walter Reed Army Institute of ResearchSandhya Vasan - Walter Reed Army Institute of ResearchGuido Ferrari - Duke Medical CenterNicolas Chomont - Centre Hospitalier de l’Université de MontréalLydie Trautmann - Oregon Health & Science UniversityRV254 and RV304 Study Groups
- Contributors
- Daniel Sauter (Editor)
- Publication Details
- Journal of virology, v 99(3)
- Publisher
- American Society for Microbiology
- Number of pages
- 25
- Grant note
- Chulalongkorn UniversityArmed Forces Research Institute of Medical Sciences (AFRIMS)Institute of HIV Research and Innovation (IHRI)Faculty of Medicine, Chulalongkorn UniversityHenry M. Jackson Foundation for the Advancement of Military MedicineThai Government Pharmaceutical Organization (GPO)ViiV Healthcare
We thank our study participants and staff from SEARCH, the Thai Red Cross AIDS Research Centre (TRC-ARC), Chulalongkorn University, and the Armed Forces Research Institute of Medical Sciences (AFRIMS) for their valuable contributions to this study. We thank the members of the RV254 and RV304 study groups, including Nipat Teeratakulpisarn, Somchai Sriplienchan, Ponpen Tantivitayakul, Nitiya Chomchey, Duanghathai Suttichom, Kultida Poltavee, Jintana Intasan, Tassanee Luekasemsuk, Hathairat Savadsuk, Somporn Tipsuk, Suwanna Puttamsawin, Kamonkan Tangnaree, Chutharat Munkong, and Rommanus Thaimanee from the Institute of HIV Research and Innovation (IHRI); Supanit Pattanachaiwit, Patcharin Eamyoung, and Sasiwimol Ubolyam from the Thai Red Cross AIDS Research Centre; Sukalya Lerdlum, Rungsun Rerknimitr, Sunee Sirivichayakul, and Phandee Wattanaboonyongcharoen from the Faculty of Medicine, Chulalongkorn University; Robert O'Connell, Alexandra Schuetz, Siriwat Akapirat, Nantana Tantibul, Nampueng Churikanont, and Saowanit Getchalarat from the Armed Forces Research Institute of Medical Sciences in Bangkok; and Trevor Crowell, Donn Colby, Ellen Turk, Oratai Butterworth, Mark Milazzo, and Leigh Anne Eller from the U.S. Military HIV Research Program and Henry M. Jackson Foundation for the Advancement of Military Medicine. We are grateful to the Thai Government Pharmaceutical Organization (GPO), ViiV Healthcare, Gilead Sciences, and Merck for providing the antiretroviral medications for this study.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Infectious Diseases (and HIV Medicine)
- Web of Science ID
- WOS:001418185300001
- Scopus ID
- 2-s2.0-105000954162
- Other Identifier
- 991022027423104721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Virology