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

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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.