Neutralization activity in chronic HIV infection is characterized by a distinct programming of follicular helper CD4 T cells.

Autor:	Moysi E; Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA., Sharma AA; Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA., O'Dell S; Virology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA., Georgakis S; Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Del Rio Estrada PM; Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.; Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias 'Ismael Cosío Villegas', Mexico City, Mexico., Torres-Ruiz F; Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias 'Ismael Cosío Villegas', Mexico City, Mexico., Navarro MG; Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias 'Ismael Cosío Villegas', Mexico City, Mexico, Subdireccion de Otorrinolaringologia, Instituto Nacional de Rehabilitación 'Luis Guillermo Ibarra Ibarra'., Villalobos YAL; Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias 'Ismael Cosío Villegas', Mexico City, Mexico., Rios SA; Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias 'Ismael Cosío Villegas', Mexico City, Mexico., Reyes-Teran G; Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City, Mexico., Beddall MH; ImmunoTechnology Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA., Ko SH; Virus Persistence and Dynamics Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA., Belinky F; Virus Persistence and Dynamics Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA., Orfanakis M; Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., de Leval L; Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Enriquez AB; Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA., Buckner CM; Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD, USA., Moir S; Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD, USA., Doria-Rose N; Virology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA., Boritz E; Virus Persistence and Dynamics Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA., Mascola JR; Virology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA.; ModeX Therapeutics, Weston, MA, USA., Sekaly RP; Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA., Koup RA; Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA., Petrovas C; Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA.; Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Aug 03. Date of Electronic Publication: 2024 Aug 03.
DOI:	10.1101/2024.07.31.605954
Abstrakt:	A subset of people living with HIV (PLWH) can produce broadly neutralizing antibodies (bNAbs) against HIV, but the lymph node (LN) dynamics that promote the generation of these antibodies are poorly understood. Here, we explored LN-associated histological, immunological, and virological mechanisms of bNAb generation in a cohort of anti-retroviral therapy (ART)-naïve PLWH. We found that participants who produce bNAbs, termed neutralizers, have a superior LN-associated B cell follicle architecture compared with PLWH who do not. The latter was associated with a significantly higher in situ prevalence of Bcl-6 hi follicular helper CD4 T cells (TFH), expressing a molecular program that favors their differentiation and stemness, and significantly reduced IL-10 follicular suppressor CD4 T cells. Furthermore, our data reveal possible molecular targets mediating TFH- B cell interactions in neutralizers. Together, we identify cellular and molecular mechanisms that contribute to the development of bNAbs in PLWH. Competing Interests: Disclosure of Conflicts of Interest The authors declare no competing conflicts of interest.
Databáze:	MEDLINE
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