Evidence implicating Gfi-1 and Pim-1 in pre-T-cell differentiation steps associated with beta-selection.
After rearrangement of the T-cell receptor (TCR) beta-locus, early CD4(-)/CD8(-) double negative (DN) thymic T-cells undergo a process termed 'beta-selection' that allows the preferential expansion of cells with a functional TCR beta-chain. This process leads to the formation of a rapidly cycling subset of DN cells that subsequently develop into CD4(+)/CD8(+) double positive (DP) cells. Using transgenic mice that constitutively express the zinc finger protein Gfi-1 and the serine/threonine kinase Pim-1, we found that the levels of both proteins are important for the correct development of DP cells from DN precursors at the stage where 'beta-selection' occurs. Analysis of the CD25(+)/CD44(-,lo) DN subpopulation from these animals revealed that Gfi-1 inhibits and Pim-1 promotes the development of larger beta-selected cycling cells ('L subset') from smaller resting cells ('E subset') within this subpopulation. We conclude from our data that both proteins, Pim-1 and Gfi-1, participate in the regulation of beta-selection-associated pre-T-cell differentiation in opposite directions and that the ratio of both proteins is important for pre-T-cells to pass the 'E' to 'L' transition correctly during beta-selection.
Schmidt
T
T
Institut für Zellbiologie (Tumorforschung), IFZ, Universitätsklinikum Essen, Virchowstrasse 173, D-45122 Essen, Germany.
Karsunky
H
H
Rödel
B
B
Zevnik
B
B
Elsässer
H P
HP
Möröy
T
T
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D003433:Crosses, Genetic; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins / Q000032:analysis / Q000502:physiology*; D015329:Gene Rearrangement, T-Lymphocyte; D019254:Genes, bcl-2; D018960:Hyaluronan Receptors / Q000032:analysis; D019891:Leukopoiesis; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000032:analysis; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000502:physiology*; D051573:Proto-Oncogene Proteins c-pim-1; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D013950:Thymus Gland; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
D015704:CD4 Antigens; D016827:CD8 Antigens; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; D018960:Hyaluronan Receptors; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C496636:Pim1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1