Normal T-cell development and immune functions in TRIM-deficient mice.
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.
Kölsch
Uwe
U
Institute of Immunology, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany.
Arndt
Börge
B
Reinhold
Dirk
D
Lindquist
Jonathan A
JA
Jüling
Nicole
N
Kliche
Stefanie
S
Pfeffer
Klaus
K
Bruyns
Eddy
E
Schraven
Burkhart
B
Simeoni
Luca
L
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
D017252:CD3 Complex; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C510344:TRIM protein, mouse; D014443:Tyrosine; D051058:Oncogene Protein v-akt