GAMMADELTA HOMING · Analysis of the mechanisms that direct gamma-delta T cell homing and function.
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2007-04-01 → 2008-03-31
- EU contribution
- €40,000
- Participants
- 1
- Scheme
- EIF
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Results in brief
Final Activity Report Summary - GAMMADELTA HOMING (Analysis of the mechanisms that direct gamma-delta T cell homing and function)
The host Institute of Immunology at the Hannover Medical School under the direction of Prof. Dr Reinhold Förster has an outstanding record in the field of leukocyte migration. Moreover, the department of Prof. Dr Reinhold Förster is firmly connected to the main research and education networks in the area of Hannover. The fellow, Dr Immo Prinz, had during his EIF Marie Curie fellowship in France worked in the field of unconventional T cells, in particular gamma-delta T cells. During that period, which was hosted by Dr Bernard Malissen at the Centre d'Immunologie de Marseille-Luminy, he had developed a mouse model that simplifies the analysis of gamma-delta T cells. The scientific objectives of this European Re-integration Grant were to investigate the homing and migration properties of gamma-delta T cells. Therefore, the aforementioned and other mouse models were transferred to the Institute of Immunology in Hannover. Now combining the scientific and technical excellence of the host laboratory in the field of leukocyte migration and the sophisticated mouse models generated during the EIF fellowship, we have started to thoroughly investigate the homing and migration properties of gamma-delta T cells. Our first results show that this undertaking is feasible and that it will advance our understanding of gamma-delta T cell biology. The formal objective of this European Re-integration Grant was to effectively re-integrate the fellow into the German biomedical research landscape. This goal has been accomplished by providing the fellow Dr Immo Prinz with a three year contract to establish his own research group within the department of Immunology. In this situation, the 12 months support of the Marie Curie ERG served as valuable start-up funding. Future continuation of this research project is now assured, because Dr Immo Prinz has during his first year in Hannover managed to obtain two research grants to support his research at the Hannover Medical School beyond this period.
Data: CORDIS, © European Union
Project objective
The genes coding for the alpha, beta, gamma and delta T cell receptor (TCR) chains were cloned over 20 years ago. However, still relatively little is known about T cells that utilize the gamma-delta TCR. Particularly the biological functions of gamma-delta T cells and the mechanisms that govern their homing to specific epithelial tissues remain enigmatic.In the blood and in secondary lymphoid organs, only 1% to 3 % of the T cells are gamma-delta T cells. In contrast, gamma-delta T cells are disproportionately enriched in various epithelial tissues, where they often constitute the majority of the intraepithelial lymphocytes (IELs).Specific subsets of gamma-delta T cells with tissue-specific semi-invariant TCR repertoires reside in the epithelia of the skin, the small intestine, the vagina/reproductive tract, the decidua, the lung/respiratory tract, and in the nasal mucosa. In the proposed work we will investigate the function and tissue homing properties of the TCR gamma-delta + IELs found in various epithelial tissues.To date, such analysis is hampered by two circumstances:- First, the only gamma-delta T cell specific marker in the human or mouse system is the gamma-delta TCR itself. Therefore, detection of gamma-delta T cells with monoclonal antibodies (mAb) specific gamma-delta TCR for their will activate the cells and will obstruct further analysis.- Second, activated gamma-delta T cells often down-regulate their TCR to non-detectable levels. To circumvent these obstacles, I have developed, during my Marie Curie fellowship in the laboratory of Dr.Bernard Malissen, a novel targeting approach that allows the direct identification of gamma-delta T cells in vivo without prior manipulation (Prinz et al., 2006, Nature Immunology, in press). I will use this model during the reintegration period to investigate the mechanisms that direct gamma-delta T cell homing and function.
Original text from CORDIS.
Participants
- MEDIZINISCHE HOCHSCHULE HANNOVER HANNOVER MEDICAL SCHOOL · HANNOVERCoordinatorCity levelGermany
Links
Data: CORDIS, © European Union
