title: Normal T-cell development and immune functions in TRIM-deficient mice.
abstract: 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.
authors.affiliation: Institute of Immunology, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Kölsch
authors.forename: Börge
authors.initials: B
authors.lastname: Arndt
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhold
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Lindquist
authors.forename: Nicole
authors.initials: N
authors.lastname: Jüling
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kliche
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfeffer
authors.forename: Eddy
authors.initials: E
authors.lastname: Bruyns
authors.forename: Burkhart
authors.initials: B
authors.lastname: Schraven
authors.forename: Luca
authors.initials: L
authors.lastname: Simeoni
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D049628:Body Size / Q000235:genetics; D017252:CD3 Complex / Q000032:analysis; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002462:Cell Membrane / Q000276:immunology; D049109:Cell Proliferation; D004789:Enzyme Activation; D008213:Lymphocyte Activation / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D051058:Oncogene Protein v-akt / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C510344:TRIM protein, mouse; D014443:Tyrosine; D051058:Oncogene Protein v-akt