Evidence implicating Gfi-1 and Pim-1 in pre-T-cell differentiation steps associated with β-selection

Abstract

After rearrangement of the T-cell receptor (TCR) β-locus, early CD4-/CD8- double negative (DN) thymic T-cells undergo a process termed 'β-selection' that allows the preferential expansion of cells with a functional TCR β-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 (β-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 β-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 β-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 β-selection.