Follicular Immune Landscaping Reveals a Distinct Profile of FOXP3<sup>hi</sup>CD4<sup>hi</sup> T Cells in Treated Compared to Untreated HIV
Spiros Georgakis,
Michail Orfanakis,
Cloe Brenna,
Simon Burgermeister,
Perla M. Del Rio Estrada,
Mauricio González-Navarro,
Fernanda Torres-Ruiz,
Gustavo Reyes-Terán,
Santiago Avila-Rios,
Yara Andrea Luna-Villalobos,
Oliver Y. Chén,
Giuseppe Pantaleo,
Richard A. Koup,
Constantinos Petrovas
Affiliations
Spiros Georgakis
Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital, University of Lausanne, Rue du Bugnon 25, CH-1011 Lausanne, Switzerland
Michail Orfanakis
Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital, University of Lausanne, Rue du Bugnon 25, CH-1011 Lausanne, Switzerland
Cloe Brenna
Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital, University of Lausanne, Rue du Bugnon 25, CH-1011 Lausanne, Switzerland
Simon Burgermeister
Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital, University of Lausanne, Rue du Bugnon 25, CH-1011 Lausanne, Switzerland
Perla M. Del Rio Estrada
Centro de Investigacion en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City 14080, Mexico
Mauricio González-Navarro
Centro de Investigacion en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City 14080, Mexico
Fernanda Torres-Ruiz
Centro de Investigacion en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City 14080, Mexico
Gustavo Reyes-Terán
Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Secretaría de Salud de México, Mexico City 14610, Mexico
Santiago Avila-Rios
Centro de Investigacion en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City 14080, Mexico
Yara Andrea Luna-Villalobos
Centro de Investigacion en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City 14080, Mexico
Oliver Y. Chén
Department of Laboratory Medicine and Pathology, Faculty of Biology and Medicine, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland
Giuseppe Pantaleo
Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, CH-1011 Lausanne, Switzerland
Richard A. Koup
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Constantinos Petrovas
Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital, University of Lausanne, Rue du Bugnon 25, CH-1011 Lausanne, Switzerland
Follicular helper CD4hi T cells (TFH) are a major cellular pool for the maintenance of the HIV reservoir. Therefore, the delineation of the follicular (F)/germinal center (GC) immune landscape will significantly advance our understanding of HIV pathogenesis. We have applied multiplex confocal imaging, in combination with the relevant computational tools, to investigate F/GC in situ immune dynamics in viremic (vir-HIV), antiretroviral-treated (cART HIV) People Living With HIV (PLWH) and compare them to reactive, non-infected controls. Lymph nodes (LNs) from viremic and cART PLWH could be further grouped based on their TFH cell densities in high-TFH and low-TFH subgroups. These subgroups were also characterized by different in situ distributions of PD1hi TFH cells. Furthermore, a significant accumulation of follicular FOXP3hiCD4hi T cells, which were characterized by a low scattering in situ distribution profile and strongly correlated with the cell density of CD8hi T cells, was found in the cART-HIV low-TFH group. An inverse correlation between plasma viral load and LN GrzBhiCD8hi T and CD16hiCD15lo cells was found. Our data reveal the complex GC immune landscaping in HIV infection and suggest that follicular FOXP3hiCD4hi T cells could be negative regulators of TFH cell prevalence in cART-HIV.
