Biology subjects

Schulz, A. R.

Publications and source records attributed to Schulz, A. R..

3 recordsLinked to original sources

bioRxiv2023

Multimodal profiling of peripheral blood identifies proliferating circulating effector CD4+ T cells as predictors for response to integrin α4β7-blocking therapy in patients with inflammatory bowel disease

Despite the success of biological therapies in inflammatory bowel disease (IBD), patient management remains challenging due to a lack of therapy response predictors. Here we prospectively sampled two cohorts of IBD patient cohorts receiving the anti-integrin 4{beta}7 antibody vedolizumab. Samples were subjected to mass cytometry, single-cell RNA sequencing, single-cell V(D)J sequencing, serum proteomics, and multidimensional flow cytometry to comprehensively assess vedolizumab-induced immunological changes in the peripheral blood and their potential associations with treatment response. Vedolizumab induced changes in the abundance of both circulating innate and adaptive immune cell compartments and modified the T cell receptor diversity of circulating gut-homing CD4+ memory T cells. Through integration of multimodal parameters and machine learning, we identify that pretreatment activated proliferating CD4+ memory T cell abundance is associated with treatment failure, independent of clinical variables, thereby providing a reliable predictive classifier with significant implications for the personalized management of IBD patients.

immunology↗

bioRxiv2022

SARS-CoV-2 specific plasma cells acquire the phenotype of long-lived plasma cells in the human bone marrow

Establishment of long-lived plasma cells (PC) in the bone marrow (BM) is important for the development of long-term specific humoral immunity. While SARS-CoV-2-specific, resting, affinity-matured, IgG-secreting plasma cells were described in human bone marrow approx. 6-7 months after infection or vaccination, the long-term durability of these PC remains unclear. We here show that approximately 20% of SARS-CoV-2-specific human BM plasma cells, including RBD-specific PC accommodate the phenotype of long-lived plasma cells, characterized by the lack of CD19 and/or CD45. This result provides evidence in support of the emergence of persistent SARS-CoV-2 specific plasma cells in humans sustaining the durable production of specific serum IgG protecting against severe courses of COVID-19.

immunology↗

bioRxiv2020

Mobilization of tissue-resident memory CD4+ T lymphocytes and their contribution to a systemic secondary immune reaction

While it is generally accepted that tissue-resident memory T lymphocytes protect host tissues from secondary immune challenges, it is unclear whether, and if so, how they contribute to systemic secondary immune responses. Here we show that in human individuals with an established immune memory to measles, mumps and rubella viruses, when challenged with the measles-mumps-rubella (MMR) vaccine again, tissue-resident memory CD4+ T cells are mobilized into the blood within 16 to 48 hours after vaccination. These cells then leave the blood again, and apparently contribute to the systemic secondary immune reaction, as is evident from the representation of mobilized T cell receptor V{beta} clonotypes among newly generated circulating memory T lymphocytes, from day 7 onwards. Mobilization of the tissue-resident memory T cells is cognate, in that memory T lymphocytes recognizing other antigens, e.g. tetanus toxin, are not mobilized, unless they cross-react with the vaccine. These data originally demonstrate the essential contribution of tissue-resident memory T cells to secondary systemic immune responses, confirming that immunological memories to systemic pathogens are maintained (also) by tissue-resident memory T cells. In practical terms, the present work defines day 1 to 2 after antigenic challenge as a time window to assess the entire immunological T cell memory for a certain pathogen, including mobilized tissue-resident memory T cells, and its correlates of effectivity. Capsule summaryThe study demonstrates the rapid and cognate mobilization of tissue-resident memory CD4+ T cells into the blood upon antigenic rechallenge, and their contribution to secondary systemic immune responses.

immunology↗