MHC-Independent Genetic Factors Control the Magnitude of CD4+ T Cell Responses to Amyloid- Peptide in Mice through Regulatory T Cell-Mediated Inhibition
| Autor: | Maria Manuel Nunes, Pierre Aucouturier, Cécile Toly-Ndour, Gabrielle Lui, Guillaume Dorothée, Martine Bruley-Rosset |
|---|---|
| Přispěvatelé: | Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), This work was supported by grants from Association France Alzheimer, Fondation de France, Universite´ Pierre et Marie Curie, and INSERM., Aucouturier, Pierre, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU) |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
CD4-Positive T-Lymphocytes
[SDV.IMM] Life Sciences [q-bio]/Immunology Regulatory T cell Transgene T cell Immunology Molecular Sequence Data [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health Congenic Dose-Response Relationship Immunologic Epitopes T-Lymphocyte Mice Transgenic Major histocompatibility complex T-Lymphocytes Regulatory Epitope 03 medical and health sciences Mice 0302 clinical medicine Alzheimer Disease medicine Immunology and Allergy Cytotoxic T cell Animals Humans Amino Acid Sequence Alleles 030304 developmental biology 0303 health sciences MHC class II Mice Inbred BALB C Amyloid beta-Peptides biology [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology H-2 Antigens Histocompatibility Antigens Class II Peptide Fragments 3. Good health Mice Inbred C57BL medicine.anatomical_structure Mice Inbred DBA [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health biology.protein Mice Inbred CBA [SDV.IMM]Life Sciences [q-bio]/Immunology 030215 immunology |
| Zdroj: | Journal of Immunology Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2011, 187 (9), pp.4492-4500. ⟨10.4049/jimmunol.1003953⟩ Journal of Immunology, 2011, 187 (9), pp.4492-4500. ⟨10.4049/jimmunol.1003953⟩ |
| ISSN: | 0022-1767 1550-6606 |
| DOI: | 10.4049/jimmunol.1003953⟩ |
| Popis: | Accumulation of amyloid-β peptide (Aβ) is considered the triggering factor of pathogenic lesions in Alzheimer’s disease (AD), and vaccines targeting Aβ are promising therapeutic options. However, the occurrence of meningoencephalitides attributed to T cell responses in 6% of Aβ-immunized patients underscores the need for a better understanding of T cell responses to Aβ. We characterized the parameters controlling the magnitude of Aβ-specific CD4+ T cell responses in mice. T cell responsiveness to Aβ1-42 was highly heterogeneous between mouse strains of different H-2 haplotypes, with SJL/J (H-2s) mice displaying a strong response, mainly specific for Aβ10-24, and C57BL/6 (H-2b) mice displaying a weak response to Aβ16-30. Surprisingly, C57BL/6 mice congenic for the H-2s haplotype (B6.H-2S), which display a “permissive” MHC class II allele for presentation of the immunodominant Aβ10-24 epitope, showed a very weak CD4+ T cell response to Aβ, suggesting that MHC-independent genes downmodulate Aβ-specific CD4+ T cell responses in C57BL/6 background. Vaccine-induced CD4+ T cell responses to Aβ were significantly enhanced in both C57BL/6 and B6.H-2S mice upon depletion of regulatory T cells (Tregs), whereas Treg-depleted SJL/J mice displayed unaltered Aβ-specific T cell responses. Finally, Treg depletion in C57BL/6 transgenic APPPS1 mice, a mouse model of AD, results in enhanced vaccine-induced CD4+ T cell responses in AD compared with wild-type animals. We concluded that the magnitude of Aβ-specific CD4+ T cell responses is critically controlled in both physiological and pathological settings by MHC-independent genetic factors that determine the overall potency of Aβ-specific Treg responses. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|