Cargando…

Identification and characterization of antigen-specific CD4(+) T cells targeting renally expressed antigens in human lupus nephritis with two independent methods

In the search for anti-renal autoreactivity in human lupus nephritis, we stimulated blood-derived CD4(+) T cells from patients with systemic lupus erythematosus with various kidney lysates. Although only minor responses were detectable, these experiments led to the development of a search algorithm...

Descripción completa

Detalles Bibliográficos
Autores principales: Tesch, Sebastian, Abdirama, Dimas, Grießbach, Anna-Sophie, Brand, Hannah Antonia, Goerlich, Nina, Humrich, Jens Y., Bacher, Petra, Hiepe, Falk, Riemekasten, Gabriela, Enghard, Philipp
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718878/
https://www.ncbi.nlm.nih.gov/pubmed/33277543
http://dx.doi.org/10.1038/s41598-020-78223-3
Descripción
Sumario:In the search for anti-renal autoreactivity in human lupus nephritis, we stimulated blood-derived CD4(+) T cells from patients with systemic lupus erythematosus with various kidney lysates. Although only minor responses were detectable, these experiments led to the development of a search algorithm that combined autoantibody association with human lupus nephritis and target gene expression in inflamed kidneys. Applying this algorithm, five potential T cell antigens were identified. Blood-derived CD4(+) T cells were then stimulated with these antigens. The cells were magnetically enriched prior to measurement with flow cytometry to facilitate the detection of very rare autoantigen-specific cells. The detected responses were dominated by IFN-γ-producing CD4(+) T cells. Additionally, IL-10-producing CD4(+) T cells were found. In a next step, T cell reactivity to each single antigen was independently evaluated with T cell libraries and [(3)H]-thymidine incorporation assays. Here, Vimentin and Annexin A2 were identified as the main T cell targets. Finally, Vimentin reactive T cells were also found in the urine of three patients with active disease. Overall, our experiments show that antigen-specific CD4(+) T cells targeting renally expressed antigens arise in human lupus nephritis and correlate with disease activity and are mainly of the Th1 subset.