Abstract
The rearrangement and expression of human T cell receptor (TCR)-gamma and -delta gene segments in clonal and polyclonal populations of early fetal and postnatal human TCR-gamma/delta thymocytes were examined. The data suggest that the TCR-gamma and -delta loci rearrange in an ordered and coordinated fashion. Initial rearrangements at the TCR-delta locus join V delta 2 to D delta 3, and initial rearrangements at the TCR-gamma locus join downstream V gamma gene segments (V gamma 1.8 and V gamma 2) to upstream J gamma gene segments associated with C gamma 1. These rearrangements are characterized by minimal junctional diversity. At later times there is a switch at the TCR-delta locus such that V delta 1 is joined to upstream D delta gene segments, and a switch at the TCR-gamma locus such that upstream V gamma gene segments are joined to downstream J gamma gene segments associated with C gamma 2. These rearrangements are characterized by extensive junctional diversity. Programmed rearrangement explains in part the origin of discrete subpopulations of peripheral blood TCR-gamma/delta lymphocytes that have been defined in previous studies. In addition, cytokine production by early fetal and postnatal TCR-gamma/delta 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.
Highlights
Since our analysis showed the T cell receptor (TCR) expressed by early fetal TCRy/b thymocytes to be distinct from those of postnatal TCRy/b thymocytes, we asked whether these cell populations represent functionally distinct subsets as well
We found that fetal TCR-y/b thymocyte clones were able to secrete significant levels o£ I1r4 and ID5, whereas postnatal clones did not secrete these cytokines
To begin to investigate the Va and V7 usage of these clones, the cells were incubated with mAbs that recognize epitopes encoded by different V.. and Va gene segments. 9 of 15 postnatal thymocyte clones from sample FH reacted with the 8TCS1 mAb (Table 1), indicating that these clones expressed Val-ja1 determinants [10, 45]
Summary
The fetal thymocyte samples and the samples from child thymus OM were cultured in a mixture of 20 U/ml 11,2 and 100 U/ml 11,4 for 10 d. This procedure increased the number of TCRy/6 cells from
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