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International Immunology Advance Access originally published online on March 15, 2007
International Immunology 2007 19(4):447-453; doi:10.1093/intimm/dxm009
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© The Japanese Society for Immunology. 2007. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Both Gimap5 and the diabetogenic BBDP allele of Gimap5 induce apoptosis in T cells

Ulla Dalberg, Helle Markholst and Lars Hornum

Department of Immunopharmacology, Hagedorn Research Institute, Novo Nordisk Park F6.2.30, DK-2760 Måløv, Denmark

Correspondence to: H. Markholst; E-mail: hmar{at}hagedorn.dk

Gimap5, a member of the GTPase of the immunity-associated protein family (Gimap), regulates T cell survival. A strong indication of this is found in the diabetes-prone BioBreeding rat (BBDP), where a frameshift mutation in Gimap5 results in T-cell lymphopenia. We have investigated the function of human Gimap5 in T cells. We found that reduction of Gimap5 by RNA interference in Jurkat cells did not affect the number of apoptotic cells whereas transient over-expression of Gimap5 resulted in a major increase in the number of apoptotic cells. The same effect of over-expression was found in naive human T cells purified from blood but not in activated human T cells. This suggests that the apoptosis-inducing effect of Gimap5 over-expression is dependent on the activation status of the cells. Since the apoptosis-inducing effect of Gimap5 was contrary to the expected function of Gimap5 based on the phenotype of BBDP rats, we over-expressed rat wt Gimap5 and Gimap5 with the mutation found in BBDP (Gimap5-lyp). Both versions of rat Gimap5 induced apoptosis when expressed in the rat T-cell line C58(NT)D.1.G.OVAR.1, however, Gimap5-lyp greatly exacerbated cell death. Finally, we detected the subcellular localization of Gimap5 to be at the endoplasmic reticulum and by quantitative PCR, we found that endogenous Gimap5 mRNA is up-regulated in activated T cells.

Keywords: diabetes-prone BB rat, Jurkat, Lyp, T cells

Transmitting editor: A. Cooke

Received 6 October 2006, accepted 18 January 2007.


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