Control of regulatory T cells is necessary for vaccine-like effects of antiviral immunotherapy by monoclonal antibodies
| Autor: | Mireia Pelegrin, Marc Piechaczyk, Marc Plays, Roudaina Nasser, Laurent Gros |
|---|---|
| Přispěvatelé: | Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM) |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Mice
129 Strain medicine.drug_class medicine.medical_treatment Immunology chemical and pharmacologic phenomena Context (language use) Biology Monoclonal antibody Antibodies Viral Lymphocyte Activation Biochemistry Immunotherapy Adoptive T-Lymphocytes Regulatory 03 medical and health sciences Mice 0302 clinical medicine Immune system Immunity medicine Cytotoxic T cell Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology 030304 developmental biology 0303 health sciences Immunity Cellular Antibodies Monoclonal Viral Vaccines Cell Biology Hematology Immunotherapy 3. Good health Immunity Humoral Interleukin-10 Interleukin 10 CTL Disease Models Animal 030215 immunology Retroviridae Infections T-Lymphocytes Cytotoxic |
| Zdroj: | Blood Blood, American Society of Hematology, 2013, 121 (7), pp.1102--11. ⟨10.1182/blood-2012-06-432153⟩ |
| ISSN: | 0006-4971 1528-0020 |
| DOI: | 10.1182/blood-2012-06-432153⟩ |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|