„Multiparameter characterization of surveillance of reproductive epithelium homeostasis by gamma-delta T cells that includes high resolution intravital microscopy”
(acronym: SONATA_TGD)

Project supported by the National Science Centre, Poland under the „SONATA BIS 4” programme

Total cost: 1 997 904,00 PLN
Centre Contribution: 1 340 184,00 PLN
Duration: 01/07/2015 – 30/06/2020

Principal Investigator: dr Grzegorz Chodaczek
Project Consortium:

  1. Wrocławskie Centrum Badań EIT+ Sp. z o.o. – Consortium Leader
  2. Instytut Immunologii i Terapii Doświadczalnej im. Ludwika Hirszfelda PAN

The aim of the project is to analyze mechanisms of immune surveillance of reproductive mucosa with a focus on activity of γδ T cell receptor (TCR)-expressing lymphocytes. Proposed studies will be conducted using novel imaging approaches by employing high resolution confocal microscopy and intravital microscopy. In order to comprehensively characterize the immune surveillance which is required for epithelial homeostasis maintenance during infection or wounding the proposed in situ analysis will be supported by advanced ex vivo techniques. Among many cell types engaged in the process of mucosal surveillance γδ T cell play a unique role. The prevailing view in the mucosal immunology is that γδ T lymphocytes maintain tissue homeostasis by recognizing self-antigens which are expressed upon wounding or infection. In contrast, applicant’s own published research, which utilized a novel technique being a combination of intravital confocal microscopy with immunofluorescence (Chodaczek et al. Nature Immunology 2012), shows that skin γδ T lymphocytes are in a permanent state of heightened activation through constitutive γδ TCR phosphorylation, which immobilizes them in epidermis suggesting continuous presence of a cognate ligand in healthy tissue. It is not known whether similar mechanisms apply to other epithelia hosting similar γδ T cell populations. The immune surveillance of reproductive mucosa is poorly studied, in spite of many years of research devoted to solving mechanisms of immunity against HIV. The project aims at filling the gap in knowledge through 1) analysis of activation status of intraepithelial T cells, 2) analysis of epithelial functions and induction of immune responses modulated by intraepithelial T cells, 3) visualization of epithelial leukocyte dynamics in real time including cell motility and cellular interactions.