Asymmetric T cell division of GAD65 specific naive T cells contribute to an early divergence in the differentiation fate into memory T cell subsets.

Autor: Alampi G; San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., Vignali D; San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., Centorame I; San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., Canu A; San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., Cosorich I; San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., Filoni J; San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., Di Dedda C; San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., Monti P; San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
Jazyk: angličtina
Zdroj: Immunology [Immunology] 2022 Nov; Vol. 167 (3), pp. 303-313. Date of Electronic Publication: 2022 Jul 26.
DOI: 10.1111/imm.13537
Abstrakt: Autoreactive T cells with the phenotype and function of different memory subsets are present in patients who developed type 1 diabetes (TID). According to the progressive differentiation model, memory subsets generate from naïve precursors in a linear and unidirectional path depending on the strength and quality of stimulatory signals. By observing human naïve T cells in contact with GAD65 loaded autologous dendritic cells, we observed that approximately 10% of cells divided with the plane of cell division parallel to the one of the immune synapse, causing phenotypic asymmetries in the proximal and distal daughter T cells. After the first T cell division, proximal and distal daughter T cells showed different phenotype, metabolic signature and commitment to differentiate towards long-lived memory T cells or T cells with effector function. Subjects with or without T1D showed a similar frequency of asymmetric T cell division (ATCD) for autoantigens and recall antigens specific T cells, however the frequency of ATCD is significantly increased in autoreactive T cells in patients with T1D when IL-7 was added to the culture. An increased upregulation of GLUT1 in response to IL-7 in patients with T1D was related to the rate of ATCD. Our results showed that ATCD is associated with an early divergence in the differentiation fate of naïve T cells specific for GAD65 during first antigen encounter.
(© 2022 The Authors. Immunology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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