Dr Sophie Rutschmann

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 project is an active collaboration with Prof. Philip Ashton-Rickardt in the department of Immunology. This unbiased approach is, to date, the only way to identify new genes and new genes' function in a phenomenon of interest. We are currently creating ethyl-n-nitrosourea (ENU) germline mutant lines which are individually screened for their CD8 T cell immune response to virus in an in vivo model of infection. Mutations affecting the development, contraction and long-term maintenance of anti-viral CD8 T cells will be isolated and positionaly cloned. The effect of the mutations on CD8 T cells' immune response and the immune system in general will be thoroughly characterise

Students

• Miss Onjee Choi (onjee.choi06@imperial.ac.uk)
• Dr. Isobel Okoye (i.okoye@imperial.ac.uk)
• Dr. Phillip J Mueller (p.muller@imperial.ac.uk)
• Dr. Lihui Wang

Enquiries with CV welcome

Selected Publications

Rutschmann S, Brandl K, Li X, Du X, Xiao N, Schnabl B, Brenner DA, Beutler B. (Epub 2009 Feb 6.) Enhanced sensitivity to DSS colitis caused by a hypomorphic Mbtps1 mutation disrupting the ATF6-driven unfolded protein response. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3300-5.

Croker BA; Lawson BR; Rutschmann S; Berger M; Eidenschenk C; Blasius AL; Moresco EM; Sovath S; Cengia L; Shultz LD; et al. (30 Sep 2008). Inflammation and autoimmunity caused by a SHP1 mutation depend on IL-1, MyD88, and a microbial trigger. Proc Natl Acad Sci U S A. 105:15028-15033.

Rutschmann S; Hoebe K. (Apr 2008). Dissecting innate immunity by germline mutagenesis. Immunology. 123:459-468.

Crozat K; Hoebe K; Ugolini S; Hong NA; Janssen E; Rutschmann S; Mudd S; Sovath S; Vivier E; Beutler B. (16 Apr 2007). Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis. J Exp Med. 204:853-863.

Janssen E; Tabeta K; Barnes MJ; Rutschmann S; McBride S; Bahjat KS; Schoenberger SP; Theofilopoulos AN; Beutler B; Hoebe K. (Jun 2006). Efficient T cell activation via a Toll-Interleukin 1 Receptor-independent pathway. Immunity. 24:787-799.

Rutschmann S; Hoebe K; Zalevsky J; Du X; Mann N; Dahiyat BI; Steed P; Beutler B. (15 Jun 2006). PanR1, a dominant negative missense allele of the gene encoding TNF-alpha (Tnf), does not impair lymphoid development. J Immunol. 176:7525-7532.

Beutler B; Jiang Z; Georgel P; Crozat K; Croker B; Rutschmann S; Du X; Hoebe K. (2006). Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large. Annu Rev Immunol. 24:353-389.

Hoebe K; Georgel P; Rutschmann S; Du X; Mudd S; Crozat K; Sovath S; Shamel L; Hartung T; Zähringer U; et al. (03 Feb 2005). CD36 is a sensor of diacylglycerides. Nature. 433:523-527.

Gobert V; Gottar M; Matskevich AA; Rutschmann S; Royet J; Belvin M; Hoffmann JA; Ferrandon D. (19 Dec 2003). Dual activation of the Drosophila toll pathway by two pattern recognition receptors. Science. 302:2126-2130.

Rutschmann S; Jung AC; Zhou R; Silverman N; Hoffmann JA; Ferrandon D. (Oct 2000). Role of Drosophila IKK gamma in a toll-independent antibacterial immune response. Nat Immunol. 1:342-347.

Rutschmann S; Jung AC; Hetru C; Reichhart JM; Hoffmann JA; Ferrandon D. (May 2000). The Rel protein DIF mediates the antifungal but not the antibacterial host defense in Drosophila. Immunity. 12:569-580.