title: Control of regulatory T cells is necessary for vaccine-like effects of antiviral immunotherapy by monoclonal antibodies.
abstract: Regulatory T cells (Tregs) down-regulate immunity and are associated with chronic viral infections, suggesting that their inhibition might be used to treat life-threatening diseases. Using the FrCasE mouse retroviral model, we have recently shown that short mAb-based immunotherapies can induce life-long protective immunity. This finding has a potentially important therapeutical impact because mAbs are increasingly used to treat severe viral infections. We now report that poor anti-FrCasE immunity in infected mice is due to Treg expansion in secondary lymphoid organs because depletion of Tregs restored humoral and cytotoxic T lymphocyte (CTL) antiviral responses. Kinetic analyses show that Treg expansion is not a consequence of chronicity, but rather is associated with viral spread. Moreover, Treg adoptive transfers indicate that production of the immunosuppressive cytokine IL-10 is essential for preventing a protective immune response. Finally, treatment of infected mice with a virus-neutralizing IgG2a shortly after infection prevents Treg expansion and limits immunosuppressive activity. This effect is rapid, necessary for the development of protective immunity, and depends on mAb effector functions. Therefore, manipulating Tregs may be necessary to confer robust antiviral immunity in the context of mAb-based therapy. This concept likely applies to cancer treatment because vaccine-like effects of mAbs have also been observed in certain cancer immunotherapies.
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Unité Mixte de Recherche (UMR) 5535, Centre National de la Recherche Scientifique, Montpellier, France.
authors.forename: Roudaina
authors.initials: R
authors.lastname: Nasser
authors.forename: Mireia
authors.initials: M
authors.lastname: Pelegrin
authors.forename: Marc
authors.initials: M
authors.lastname: Plays
authors.forename: Laurent
authors.initials: L
authors.lastname: Gros
authors.forename: Marc
authors.initials: M
authors.lastname: Piechaczyk
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000276:immunology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D016219:Immunotherapy, Adoptive; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D057507:Mice, 129 Strain; D012192:Retroviridae Infections / Q000276:immunology* / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; C556062:IL10 protein, mouse; D014765:Viral Vaccines; D016753:Interleukin-10