Imperial College London

DrSophieRutschmann

Faculty of MedicineDepartment of Medicine

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3313 8213s.rutschmann

 
 
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Location

 

9N4bHammersmith HospitalHammersmith Campus

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Summary

 

Summary

Genetics of memory T cells

Immunological memory provides improved long-term protection against re-infection by previously encountered pathogens. Upon acute viral infection, pathogen-specific T lymphocytes multiply rapidly and acquire effector functions that enable them to kill infected cells. This expansion phase is followed by a period of massive cell death (contraction) which eliminates more than 90% of antigen-specific T cells. The remaining 10% constitute the pool of long-term memory T lymphocytes. To become antigen-specific memory, T cells have therefore not only to escape cell death but also enter a state of quiescence to avoid replicative senescence. Despite the considerable incidence of viral infections affecting mankind worldwide and the crucial role played by memory CD8 T cells in the antiviral immune response, only a handful of genes have been shown in vivo to control the development and maintenance of memory T cells.

To identify new genes required for the development and maintenance of memory T cells, we are using an in vivo forward genetic strategy. This unbiased approach is, to date, the only way to identify new genes and new genes' function in a phenomenon of interest. We have created ethyl-n-nitrosourea (ENU) germline mutant lines which have been individually screened for their CD8 T cell immune response to virus in an in vivo model of infection. Three mutations affecting the development, contraction and long-term maintenance of anti-viral CD8 T cells have been isolated and positionaly cloned. The effect of the mutations on CD8 T cells' immune response and the immune system in general is currently being characterised.


Students

Enquiries with CV welcome

Publications

Journals

Ling GS, Crawford G, Buang N, et al., 2018, C1q restrains autoimmunity and viral infection by regulating CD8(+) T cell metabolism, Science, Vol:360, ISSN:0036-8075, Pages:558-563

Okoye I, Wang L, Pallmer K, et al., 2015, The protein LEM promotes CD8(+) T cell immunity through effects on mitochondrial respiration, Science, Vol:348, ISSN:0036-8075, Pages:995-1001

Salisbury EM, Wang L, Choi O, et al., 2014, N-Ethyl-N-nitrosourea mutagenesis in the mouse provides strong genetic and in vivo evidence for the role of the Caspase Recruitment Domain (CARD) of CARD-MAGUK1 in T regulatory cell development, Immunology, Vol:141, ISSN:0019-2805, Pages:446-456

Siggs OM, Cruite JT, Du X, et al., 2012, Disruption of copper homeostasis due to a mutation of Atp7a delays the onset of prion disease., Proc Natl Acad Sci U S A, Vol:109, Pages:13733-13738

Choi O, Heathcote DA, Ho K-K, et al., 2012, A Deficiency in Nucleoside Salvage Impairs Murine Lymphocyte Development, Homeostasis, and Survival, Journal of Immunology, Vol:188, ISSN:0022-1767, Pages:3920-3927

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