Transfection and Transcription of Genes in Developing Thymocytes

Thymocyte development is characterized by the stage-specific expression of CD4 and CD8 surface molecules (1 ). The earliest thymic immigrants, arriving from the fetal liver or bone marrow, lack CD4 and CD8 expression (CD4⁻ CD8⁻ , double negative (DN) (2 ). This population can be further subdivided into four discrete subsets defined by the differential expression of CD117 (stem cell factor, SCF, receptor; c-kit) and CD25 (IL-2Rα) (3 ). The earliest population is identified as CD117⁺ CD25⁻ , and contains precursors for T, B, and natural killer (NK) lymphocyte lineages. Induction of CD25 expression on progenitor CD117⁺ thymocytes characterizes commitment to the T cell lineage (4 ). The CD117⁺ CD25⁺ stage is also accompanied by an increased rate of cellular proliferation (5 ). Loss of CD117 expression correlates with the initiation of TCR-β gene rearrangement (6 ). Only thymocytes that successfully rearrange their TCR-β locus expand and differentiate to the next stage; this important developmental checkpoint is known as β-selection (7 ,8 ). Expression of CD25 ends with the generation of a functionally rearranged TCR-β chain, which together with the pre-TCR-α (pre-Tβ) chain forms the pre-TCR complex (9 ).