A distinct wave of human T cell receptor γ/δ lymphocytes in the early fetal thymus: Evidence for controlled gene rearrangement and cytokine production

Abstract

The rearrangement and expression of human T cell receptor (TCR)-γ and -δ gene segments in clonal and polyclonal populations of early fetal and postnatal human TCR-γ/δ thymocytes were examined. The data suggest that the TCR-γ and -δ loci rearrange in an ordered and coordinated fashion. Initial rearrangements at the TCR-δ locus join Vδ2 to Dδ3, and initial rearrangements at the TCR-γ locus join downstream Vγ gene segments (Vγ1.8 and Vγ2) to upstream Jγ gene segments associated with CγI. These rearrangements are characterized by minimal junctional diversity. At later times there is a switch at the TCR-δ locus such that Vδ1 is joined to upstream Da gene segments, and a switch at the TCR-γ locus such that upstream Vγ gene segments are joined to downstream Jγ gene segments associated with Cγ2. These rearrangements are characterized by extensive junctional diversity. Programmed rearrangement explains in part the origin of discrete subpopulations of peripheral blood TCR-γ/δ lymphocytes that have been denned in previous studies. In addition, cytokine production by early fetal and postnatal TCR-γ/δ thymocyte clones was examined. Fetal thymocyte clones produced significant levels of IL-4 and IL-5 following stimulation, whereas postnatal thymocyte clones did not produce these cytokines. Thus, these cell populations may represent functionally distinct subsets as well.