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Human alpha beta and gamma delta thymocyte development: TCR gene rearrangements, intracellular TCR beta expression, and gamma delta developmental potential--differences between men and mice
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 176(3)
- Publication Year :
- 2006
-
Abstract
- To evaluate the role of the TCR in the alphabeta/gammadelta lineage choice during human thymocyte development, molecular analyses of the TCRbeta locus in gammadelta cells and the TCRgamma and delta loci in alphabeta cells were undertaken. TCRbeta variable gene segments remained largely in germline configuration in gammadelta cells, indicating that commitment to the gammadelta lineage occurred before complete TCRbeta rearrangements in most cases. The few TCRbeta rearrangements detected were primarily out-of-frame, suggesting that productive TCRbeta rearrangements diverted cells away from the gammadelta lineage. In contrast, in alphabeta cells, the TCRgamma locus was almost completely rearranged with a random productivity profile; the TCRdelta locus contained primarily nonproductive rearrangements. Productive gamma rearrangements were, however, depleted compared with preselected cells. Productive TCRgamma and delta rearrangements rarely occurred in the same cell, suggesting that alphabeta cells developed from cells unable to produce a functional gammadelta TCR. Intracellular TCRbeta expression correlated with the up-regulation of CD4 and concomitant down-regulation of CD34, and plateaued at the early double positive stage. Surprisingly, however, some early double positive thymocytes retained gammadelta potential in culture. We present a model for human thymopoiesis which includes gammadelta development as a default pathway, an instructional role for the TCR in the alphabeta/gammadelta lineage choice, and a prolonged developmental window for beta selection and gammadelta lineage commitment. Aspects that differ from the mouse are the status of TCR gene rearrangements at the nonexpressed loci, the timing of beta selection, and maintenance of gammadelta potential through the early double positive stage of development.
- Subjects :
- Intracellular Fluid
Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor
Receptors, Antigen, T-Cell, alpha-beta
Cell Cycle
Gene Rearrangement, delta-Chain T-Cell Antigen Receptor
Models, Immunological
Infant
Cell Differentiation
Receptors, Antigen, T-Cell, gamma-delta
Thymus Gland
Coculture Techniques
Article
Mice
Organ Culture Techniques
Animals
Humans
Cell Lineage
Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
Child
Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
Subjects
Details
- ISSN :
- 00221767
- Volume :
- 176
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.pmid..........fa42875da689cc4b1b470408089cf3f7