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Panetti, C.

Publications and source records attributed to Panetti, C..

3 recordsLinked to original sources

CD4 T cells acquire innate capability upon classical T cell activation

Memory T cells, a sizable compartment of the mature immune system, enable enhanced responses upon re-infection with the same pathogen. We have recently shown that virus-experienced innate acting T (TIA) cells can modulate infectious or autoimmune diseases through TCR-independent IFN-{gamma} production. However, how these cells arise remains unclear. Here, we show that CD4 TIA cells are present in various disease settings hinting towards a disease-agnostic nature. TCR stimulation and CD28 co-stimulation are sufficient to induce naive murine and human CD4 T cells to become capable of cytokine-mediated, TCR-independent IFN-{gamma} responses. In true TIA fashion, adoptive transfer of in vitro-induced TIA cells in mice yielded a TCR-independent IFN-{gamma} response during the innate phase of a Legionella pneumophila infection. Our data thus shows that CD4 TIA cells are more ubiquitous than anticipated and could therefore be involved in more settings than expected.

immunology↗

Clonally expanded IgG antibody-secreting cells preferentially target influenza nucleoprotein following homologous and heterologous infections

Infection with influenza virus remains a significant global health concern due to its ability to acquire mutations at key antigenic sites to escape antibody recognition. While germinal center (GC) and memory B cells have been well studied following influenza infection, the clonal dynamics of antibody secreting cells (ASCs), particularly those within the bone marrow (BM) niche that are responsible for serum immune protection, remain poorly understood. Here, we combine single-cell RNA (scRNA) and B cell receptor (BCR) sequencing to characterize individual ASCs following various Influenza exposure histories. We find that BM repertories are populated by highly expanded and class-switched ASCs following Influenza infection with similar transcriptional and repertoire characteristics regardless of homologous or heterologous infection histories. By combining single-cell analysis with monoclonal antibody expression and characterization, we find that a large proportion of the expanded IgG-, but not IgA-, ASC repertoire demonstrates specificity to influenza nucleoprotein (NP). Together, our data reveal the complex relationship between BM ASC repertoires, mucosal humoral immune responses, and BCR antigen specificity during influenza infection.

immunology↗

Single-cell immune repertoire sequencing of B and T cells in murine models of infection and autoimmunity

Adaptive immune repertoires are composed by the ensemble of B and T cell receptors (BCR, TCR) within an individual and reflect both past and current immune responses. Recent advances in single-cell sequencing enable recovery of the complete adaptive immune receptor sequences in addition to transcriptional information. Such high-dimensional datasets enable the molecular quantification of clonal selection of B and T cells across a wide variety of conditions such as infection and disease. Due to costs, time required for the analysis and current practices of academic publishing, small-scale sequencing studies are often not made publicly available, despite having informative potential to elucidate immunological principles and guide future-studies. Here, we performed single-cell sequencing of B and T cells to profile clonal selection across murine models of viral infection and autoimmune disease. Specifically, we recovered transcriptome and immune repertoire information for polyclonal T follicular helper cells following acute and chronic viral infection, CD8+ T cells with binding specificity restricted to two distinct peptides of lymphocytic choriomeningitis virus, and B and T cells isolated from the nervous system in the context of experimental autoimmune encephalomyelitis. We could relate repertoire features such as clonal expansion, germline gene usage, and clonal convergence to cell phenotypes spanning activation, memory, naive, antibody secretion, T cell inflation, and regulation. Together, this dataset provides a resource for experimental and computational immunologists that can be integrated with future single-cell immune repertoire and transcriptome sequencing datasets.

immunology↗