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Molecular and Cellular Biology, May 2006, p. 3639-3648, Vol. 26, No. 9
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.9.3639-3648.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Normal T-Cell Development and Immune Functions in TRIM-Deficient Mice

Uwe Kölsch,^1, Börge Arndt,¹ Dirk Reinhold,¹ Jonathan A. Lindquist,¹ Nicole Jüling,¹ Stefanie Kliche,¹ Klaus Pfeffer,² Eddy Bruyns,³ Burkhart Schraven,¹ and Luca Simeoni^1*

Otto von Guericke University, Institute of Immunology, Leipziger Str. 44, 39120 Magdeburg,¹ FOCUS Clinical Drug Development GmbH, Im Neuenheimer Feld 515, 69120 Heidelberg,² Heinrich Heine University, Institute of Medical Microbiology, Universitätsstr. 1, 40225 Düsseldorf, Germany³

Received 2 December 2005/ Returned for modification 27 January 2006/ Accepted 13 February 2006

The transmembrane adaptor molecule TRIM is strongly expressed within thymus and in peripheral CD4⁺ T cells. Previous studies suggested that TRIM is an integral component of the T-cell receptor (TCR)/CD3 complex and might be involved in regulating TCR cycling. To elucidate the in vivo function of TRIM, we generated TRIM-deficient mice by homologous recombination. TRIM^–/– mice develop normally and are healthy and fertile. However, the animals show a mild reduction in body weight that appears to be due to a decrease in the size and/or cellularity of many organs. The morphology and anatomy of nonlymphoid as well as primary and secondary lymphoid organs is normal. The frequency of thymocyte and peripheral T-cell subsets does not differ from control littermates. In addition, a detailed analysis of lymphocyte development revealed that TRIM is not required for either positive or negative selection. Although TRIM^–/– CD4⁺ T cells showed an augmented phosphorylation of the serine/threonine kinase Akt, the in vitro characterization of peripheral T cells indicated that proliferation, survival, activation-induced cell death, migration, adhesion, TCR internalization and recycling, TCR-mediated calcium fluxes, tyrosine phosphorylation, and mitogen-activated protein family kinase activation are not affected in the absence of TRIM. Similarly, the in vivo immune response to T-dependent and T-independent antigens as well as the clinical course of experimental autoimmune encephalomyelitis, a complex Th1-mediated autoimmune model, is comparable to that of wild-type animals. Collectively, these results demonstrate that TRIM is dispensable for T-cell development and peripheral immune functions. The lack of an evident phenotype could indicate that TRIM shares redundant functions with other transmembrane adaptors involved in regulating the immune response.

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* Corresponding author. Mailing address: Institute of Immunology, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany. Phone: 49-391-6717894. Fax: 49-391-6715852. E-mail: luca.simeoni{at}medizin.uni-magdeburg.de.

Present address: Clinic of Pediatric and Neonatology, Otto von Guericke University, 39112 Magdeburg, Germany.

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Molecular and Cellular Biology, May 2006, p. 3639-3648, Vol. 26, No. 9
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.9.3639-3648.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Koelsch, U., Schraven, B., Simeoni, L. (2008). SIT and TRIM Determine T Cell Fate in the Thymus. J. Immunol. 181: 5930-5939 [Abstract] [Full Text]