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Prethymic expression of a transgenic TCR beta chain on a precursor of T-cells
G C Lincoln1, B Sheng, J Odebralski
1Department of Pathology, University of Florida College of Medicine, Health Sciences Center, Gainesville, Florida, 32610, USA.
Mice carrying a rearranged TCR Vbeta 8.2 transgene express the Vbeta protein on the vast majority of peripheral T-cells. The bone marrow and peripheral blood, as well as other lymphoid organs of both untreated animals and animals depleted of T-cells by neonatal thymectomy and/or injection from birth of monoclonal anti-TCR antibodies, contain a small population of cells that express low levels of the Vbeta transgene product, but no T-cell or other detectable lineage-specific phenotypic markers. When such TG-bearing BM cells are purified and injected directly into the non-TG thymus, they show the phenotypic maturation sequences of intrathymic T-cell development and, subsequently, mature TG-bearing peripheral T-cells. However, this population failed to support long-term recovery from lethal irradiation. Both Vbeta 8.2 TG and CD3delta mRNA transcripts are strongly expressed in the cell population, but no CD3gamma, CD3epsilon, CD3zeta, CD4, CD8beta, pre-Talpha, or RAG-1 transcript was detected. The transgene-encoded TCR component is not bound to the cell membrane exclusively by a phosphatidylinositol linkage. The data show that the fully rearranged TCR transgene and transcripts for at least one of the associated CD3 components, CD3delta, can be expressed on a subpopulation of BM and PBL cells that has not passed through the thymus. The phenotypic characteristics of this cell population resemble those described for the earliest thymocyte described by others. The TG protein molecule in this model may provide a specific developmental marker for a prothymocyte lineage subset that lacks pluripotential properties.
Mice carrying a rearranged TCR Vbeta 8.2 transgene express the Vbeta protein on the vast majority of peripheral T-cells. The bone marrow and peripheral blood, as well as other lymphoid organs of both untreated animals and animals depleted of T-cells by neonatal thymectomy and/or injection from birth of monoclonal anti-TCR antibodies, contain a small population of cells that express low levels of the Vbeta transgene product, but no T-cell or other detectable lineage-specific phenotypic markers. When such TG-bearing BM cells are purified and injected directly into the non-TG thymus, they show the phenotypic maturation sequences of intrathymic T-cell development and, subsequently, mature TG-bearing peripheral T-cells. However, this population failed to support long-term recovery from lethal irradiation. Both Vbeta 8.2 TG and CD3delta mRNA transcripts are strongly expressed in the cell population, but no CD3gamma, CD3epsilon, CD3zeta, CD4, CD8beta, pre-Talpha, or RAG-1 transcript was detected. The transgene-encoded TCR component is not bound to the cell membrane exclusively by a phosphatidylinositol linkage. The data show that the fully rearranged TCR transgene and transcripts for at least one of the associated CD3 components, CD3delta, can be expressed on a subpopulation of BM and PBL cells that has not passed through the thymus. The phenotypic characteristics of this cell population resemble those described for the earliest thymocyte described by others. The TG protein molecule in this model may provide a specific developmental marker for a prothymocyte lineage subset that lacks pluripotential properties.