TCR signal strength controls thymic differentiation of discrete proinflammatory γδ T cell subsets
| Autor: | Daniel J. Pennington, Julie C. Ribot, José R. Regueiro, Miguel Muñoz-Ruiz, Ana Rita Grosso, Ana Pamplona, Edgar Fernández-Malavé, Bruno Silva-Santos, Natacha Gonçalves-Sousa |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
T cell CD3 Cellular differentiation T-Lymphocytes Immunology Inmunología Malaria Cerebral Mice Transgenic Thymus Gland Article 03 medical and health sciences Interferon-gamma Mice 0302 clinical medicine Antigen T-Lymphocyte Subsets medicine Immunology and Allergy Cytotoxic T cell Animals Antigens Ly Humans Cells Cultured Inflammation biology T-cell receptor Interleukin-17 Cell Differentiation Receptors Antigen T-Cell gamma-delta 3. Good health Interleukin-2 Receptor beta Subunit Mice Inbred C57BL Thymocyte Disease Models Animal 030104 developmental biology medicine.anatomical_structure biology.protein Interleukin 17 030215 immunology NK Cell Lectin-Like Receptor Subfamily B Signal Transduction |
| Zdroj: | Nature Immunology Nature immunology |
| ISSN: | 1529-2908 |
| DOI: | 10.1038/ni.3424 |
| Popis: | The mouse thymus produces discrete γδ T cell subsets that make either interferon-γ (IFN-γ) or interleukin 17 (IL-17), but the role of the T cell antigen receptor (TCR) in this developmental process remains controversial. Here we show that Cd3g(+/-) Cd3d(+/-) (CD3 double-haploinsufficient (CD3DH)) mice have reduced TCR expression and signaling strength on γδ T cells. CD3DH mice had normal numbers and phenotypes of αβ thymocyte subsets, but impaired differentiation of fetal Vγ6(+) (but not Vγ4(+)) IL-17-producing γδ T cells and a marked depletion of IFN-γ-producing CD122(+) NK1.1(+) γδ T cells throughout ontogeny. Adult CD3DH mice showed reduced peripheral IFN-γ(+) γδ T cells and were resistant to experimental cerebral malaria. Thus, TCR signal strength within specific thymic developmental windows is a major determinant of the generation of proinflammatory γδ T cell subsets and their impact on pathophysiology. |
| Databáze: | OpenAIRE |
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