Dr Sophie Rutschmann

Genetics of T Cells

Immunological memory provides 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 cells constitute the pool of long-term memory T-lymphocytes. To become memory lymphocytes, T-cells have therefore not only to escape death, but also to avoid replicative senescence by entering a state of quiescence. 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 long-term maintenance of memory T-cells.

Our laboratory uses a forward genetic approach to identify the genes required for CD8 memory development and maintenance. We are currently generating ethyl-n-nitrosourea (ENU) germline mutant lines which are individually screened for their CD8 T-cell immune response in an in vivo model of viral infection. Mutations affecting the development, contraction and long-term maintenance of anti-viral CD8 T cells will be isolated and positionally cloned. The effect of the mutation on the immune response will be characterised in detail.

For further information please contact me at s.rutschmann@imperial.ac.uk

Publications:

Rutschmann S, Brandl K, Li X, Du X, Xiao N, Schnabl B, Brenner DA, Beutler B. 2009. 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. Mar 3;106(9):3300-5. Publisher weblink

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

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. Publisher weblink DOI.

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. Publisher weblink DOI.

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. Publisher weblink.