Studies on mechanisms involved in the establishment and breakdown of t-cell tolerance using t-cell receptor transgenic mice
FP4 — Training and Mobility of Researchers
- Duration
- 1997-02-01 → 1998-07-31
- EU contribution
- —
- Participants
- 2
- Scheme
- RGI
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Project objective
We propose to study molecular mechanisms underlying T cell tolerance induction and its breakdown by bacterial superantigens. We are using transgenic mice (F5) expressing a T Cell Receptor (TCR) specific for the nucleoprotein (NP) of the influenza virus crossed to mice expressing ubiquitously the NP antigen. F5/NP doubly transgenic mice in the RAG1 / background develop only anergic T cells. Those can be reactivated and acquire cytotoxic effector functionin vivo by administration of the bacterial superantigen Staphylococcal Enterotoxin A (SEA). We will a) attempt to define conditions at which reactivated T cells can lead to autoimmunity in these mice; b) study the role of TNFx in T cell tolerance and activation in F5 and F5/NP mice by crossing them to TNFx / mice and challenge them with antigenic NP peptide and SEA; c) identify and characterise genes involved in T cell tolerance using an improved version of the mRNA differential display technology. Our studies will improve the understanding of detrimental immune responses and could help in the development of strategies for clinical interventions in humans. Training content (objective, benefit and expected impact) Our goal is to better understand molecular and cellular mechanisms of establishment of T-cell tolerance and its breakdown. These studies will contribute to the development of new tools and strategies for prevention and intervention in autoimmune disorders. The projects we developp and the technics we use are improving my technical and fundamental knowledge in the field of immunology. An E.C. fellowship would give me thepossibility both to finish already promissing research projects and to accomplish my PhD thesis in a E. C. foreign country.
Original text from CORDIS.
Participants
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Data: CORDIS, © European Union