T-Regulatory Cells and Vaccination "Pay Attention and Do Not Neglect Them": Lessons from HIV and Cancer Vaccine Trials.
Efficient vaccines are characterized by the establishment of long-lived memory T cells, including T-helper (effectors and follicular) and T-regulatory cells (Tregs). While the former induces cytotoxic or antibody responses, the latter regulates immune responses by maintaining homeostasis. The role of Tregs in inflammatory conditions is ambiguous and their systematic monitoring in vaccination along with effector T-cells is not instinctive. Recent studies from the cancer field clearly showed that Tregs suppress vaccine-induced immune responses and correlate with poor clinical benefit. In HIV infection, Tregs are needed during acute infection to preserve tissue integrity from an overwhelmed activation, but are not beneficial in chronic infection as they suppress anti-HIV responses. Current assays used to evaluate vaccine-induced specific responses are limited as they do not take into account antigen-specific Tregs. However, new assays, such as the OX40 assay, which allow for the simultaneous detection of a full range of Th-responses including antigen-specific Tregs responses, can overcome these issues. In this review article we will revise the role of Tregs in vaccination and review the recent work performed in the field, including the available tools to monitor them, from novel assays to humanized mouse models.
Institut National de la Santé et de la Recherche Médicale (INSERM), U955, Equipe 16, Créteil 94000, France. vedranbrezar@gmail.com.|Faculté de médecine, Université Paris Est, Créteil 94000, France. vedranbrezar@gmail.com.|Vaccine Research Institute (VRI), Créteil 94000, France. vedranbrezar@gmail.com.
Vedran
V
Brezar
Institut National de la Santé et de la Recherche Médicale (INSERM), U955, Equipe 16, Créteil 94000, France. eronique.godot@gmail.com.|Faculté de médecine, Université Paris Est, Créteil 94000, France. eronique.godot@gmail.com.|Vaccine Research Institute (VRI), Créteil 94000, France. eronique.godot@gmail.com.
Véronique
V
Godot
Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. chengl84@email.unc.edu.
Liang
L
Cheng
Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. lishan_su@med.unc.edu.
Lishan
L
Su
Institut National de la Santé et de la Recherche Médicale (INSERM), U955, Equipe 16, Créteil 94000, France. yves.levy@aphp.fr.|Faculté de médecine, Université Paris Est, Créteil 94000, France. yves.levy@aphp.fr.|Vaccine Research Institute (VRI), Créteil 94000, France. yves.levy@aphp.fr.|AP-HP, Hôpital H. Mondor-A. Chenevier, Service d'immunologie clinique et maladies infectieuses, Créteil 94000, France. yves.levy@aphp.fr.
Yves
Y
Lévy
Institut National de la Santé et de la Recherche Médicale (INSERM), U955, Equipe 16, Créteil 94000, France. nabila.seddiki@inserm.fr.|Faculté de médecine, Université Paris Est, Créteil 94000, France. nabila.seddiki@inserm.fr.|Vaccine Research Institute (VRI), Créteil 94000, France. nabila.seddiki@inserm.fr.
Nabila
N
Seddiki
CD25; CD39; DC-based vaccine; HIV; OX40; Tregs; hu-mice; memory cell; vaccine