Search bioRxiv⌕ Search

bioRxiv · 10.1101/478164

Quantitative analysis reveals reciprocal regulations underlying recovery dynamics of thymocytes and thymic environment

Abstract

Thymic crosstalk, a set of reciprocal regulations between thymocytes and thymic environment, is relevant for orchestrating the appropriate development of thymocytes as well as the recovery of the thymus from various exogenous insults. Nevertheless, the dynamic and regulatory aspects of the thymic crosstalk have not yet been clarified. In this work, we inferred the interactions shaping the thymic crosstalk and its resultant dynamics between the thymocytes and the thymic epithelial cells (TECs) by quantitative analysis and modelling of the recovery dynamics induced by irradiation. The analysis identified regulatory interactions consistent with the known molecular evidence and revealed their dynamic roles in the recovery process. Moreover, the analysis also predicted, and a subsequent experiment verified a new regulation of CD4+CD8+ double positive (DP) thymocytes, which temporarily increases their proliferation rate upon the decrease in their population size. Our model established the pivotal step towards a dynamic understanding of the thymic crosstalk as a regulatory network system.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Kaneko, K. B., Tateishi, R., Miyao, T., Akiyama, N., Yokota, R., Akiyama, T., Kobayashi, T. J.. 2018-11-26. Quantitative analysis reveals reciprocal regulations underlying recovery dynamics of thymocytes and thymic environment. https://doi.org/10.1101/478164

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Clonally Convergent Tph/Tfh-like CD4+ T Cells are Shared Across Recovery and Recurrence in Experimental Periodontitis

Periodontitis is a chronic inflammatory disease of the tooth-supporting structures (periodontium) that requires life-long maintenance to prevent progression. Using a sensitized model of recurrent periodontitis in mice (SeRPD), in which regulatory breakdown was induced by temporary Treg depletion concurrent with disease, we mapped the gingival T cell imprint across each disease phase. Transient regulatory breakdown left a durable mucosal imprint after clinical recovery, characterized by enrichment of local and regional CD4 T cells. Paired single-cell RNA and TCR sequencing of gingival immune cells identified a convergent clonotype expanded from recovery into recurrence that carried a Tfh/Tph-like transcriptional identity. An analogous CD4 T cell population was detected in human periodontitis lesions by single-cell transcriptomics. Together, these findings support a paradigm in which clinical recovery does not ensure a local T cell repertoire reset; instead, a reservoir of antigen-experienced, tissue-adapted CD4 T cells persist in the mucosa and participate in recurrence.

immunology↗

Robust T and B cell activation is associated with rapid clearance of infectious SARS-CoV-2

The immunologic correlates of rapid clearance of SARS-CoV-2 shedding are not well understood, partly due to challenges of collecting samples early after infection and the fact that most studies do not measure infectious virus. Here, we performed mass cytometry profiling of peripheral blood cells collected from people 4-6 days after onset of symptoms from acute SARS-CoV-2 infection who underwent daily nasopharyngeal testing for SARS-CoV-2 culture positivity. We identified broad and coordinated activation of innate and adaptive immune cells in unvaccinated individuals with primary infection. Faster clearance of infectious virus shedding was associated with robust adaptive immune cell activation and proliferation, namely among cytotoxic CD8+, CD4+, and {gamma}{delta} T cells and plasmablasts. In contrast, vaccinated individuals who rapidly cleared breakthrough infection showed minimal cellular immune activation. Our findings identify early immune correlates of rapid clearance of infectious SARS-CoV-2 shedding that may inform future prevention and therapeutic approaches to reduce disease burden and transmission.

immunology↗

Live attenuated YFV-17D vaccine induces robust B and T cell immunity in vaccine-draining lymph nodes

The yellow fever virus-17D (YFV-17D) vaccine is widely regarded as one of the most effective vaccines in existence, with protection linked to robust elicitation of neutralising antibodies1. The features of the germinal centre (GC) reaction driving this durable and potent antibody responses remain unclear. Here we examined immune dynamics in blood and lymph nodes (LNs) after primary YFV-17D immunisation in humans. Using fine needle biopsy (FNB), we identified robust T and B lymphocyte responses within draining LNs, underpinning maturation of antibodies targeting the viral envelope (E). Early antibody responses were largely IgM, with gradual accumulation of E-specific memory B cells and anti-viral IgG in the subsequent months. Monoclonal antibodies derived from GC B cells had specificity for E, with diversification in the LN capable of driving increases in binding and neutralising potency. While circulating vaccine-specific CD4+ T cells peaked two weeks post-vaccination, clonally related GC and IL-10+ T follicular helper populations progressively accumulated in the LN. Comparison of FNB transcriptional datasets following YFV-17D, SARS-CoV-2 mRNA/LNP, and seasonal influenza vaccination identified a conserved GC program involving similar B and T lymphocyte subpopulations. Collectively, we find that while YFV-17D induces robust GC activity, this trait is shared with other vaccine platforms and the notably durable protection against infection may reflect an incapacity of the virus to escape host immunity.

immunology↗