CFSE · Developing quantitative methods for estimating birth and death rates of immune cells using CFSE label
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2005-12-01 → 2007-11-30
- EU contribution
- €158,326
- Participants
- 1
- Scheme
- IIF
Lines connect the coordinator with its partners.
Results in brief
Final Activity Report Summary - CFSE (Developing quantitative methods for estimating birth and death rates of immune cells using CFSE label)
Due to the development of several important experimental techniques, immunology is rapidly becoming more and more quantitative. It is now possible to track the immune responses specific to various viruses and bacteria in vivo, and more and more data are becoming available on the interactions of different types of immune cells during an immune response. Despite the widespread use of techniques of molecular biology, we are still at the beginning of our understanding of how immune responses are generated, how they are maintained and how various environmental factors may affect the rates of cell proliferation and death during an immune response. In particular, relatively little is known about the rates of proliferation and death of lymphocytes in various settings in vivo and in vitro. This research project was aimed at filling this gap. We have formulated a novel approach that can be used to estimate the rates of proliferation and death of lymphocytes in different conditions in vitro and in vivo. The approach is based on application of mathematical models of different levels of complexity to data that enumerate the number of divisions that cells in the population have undergone (CFSE data). Application of the novel mathematical models to data available via a collaboration with the laboratory of Dr Phillip Hodgkin (Walter and Elisa Hall Institute of Medical Research, Melbourne, Australia) revealed several interesting unexpected results. We have found that despite the commonly held belief, cytokine interleukin 2 (IL-2) does not affect the speed at which activated CD4+ T cells divide. However, IL-2 does affect the fraction of cells that are stimulated to participate in the response, and most importantly, IL-2 regulates how activated cells are dying during the immune response. We find that lower IL-2 concentration lead to faster rates of death of activated cells. These results challenge the widely spread view that IL-2 or T-cell growth factor regulates expansion of T cell populations by regulating cell proliferation. Similar predictions have also been generated in other experimental systems including CD8 T cells. Overall, our work forms a basis for the analysis of CFSE data, widely produced in immunology, and generates guidelines for thorough analysis of such data. We are developing tools to be used for the analysis of CFSE data; these tools are made freely available to the general public.
Data: CORDIS, © European Union
Project objective
The regulation of cell division and survival is central to immune regulation, and traditionally the analysis of these processes has been qualitative and descriptive. Recently developed techniques that allow one to follow antigen-specific T and B cells labe led with the dye CFSE over time have stimulated renewed interest in lymphocyte kinetics. Despite the widespread use of this labeling technique in immunology, the proper interpretation of labeling data is difficult and requires analysis with appropriate ma thematical models. We propose to develop efficient mathematical methods to quantify the population kinetics of lymphocytes during immune responses based on the CFSE labeling technique. For this, we plan to use the published data and are collaborating with the laboratory of Dr. Philip D. Hodgkin (Walter and Eliza Hall Institute of Medical Research, Australia), the well-known expert in CFSE labeling technique, to obtain unpublished data on the dynamics of CFSE-labeled T and B lymphocytes in vitro and in viv o. These data will be analyzed using a series of mathematical models with increased levels of complexity. These different models will be used against the data to determine how well the models can describe the data and whether such models are biologicall y realistic. The main theoretical challenge here is to develop mathematical models that are both realistic and contain minimum parameters that can be reliably estimated from the labeling data. The proposed research will allow the coordinator (VVG) to imp rove his skills in developing mathematical models of immune cell dynamics, in application of these models to experimental data, and in learning different techniques of estimation of model parameters. The proposed research will likely result in development of a group of researchers in EU with expertise in the several areas of theoretical immunology including the analysis of data obtained from the dynamics of CFSE labeled lymphocytes.
Original text from CORDIS.
Participants
- UNIVERSITEIT UTRECHT · UTRECHTCoordinatorNetherlands
Links
Data: CORDIS, © European Union