Thymic epithelial cells induce in vitro differentiation of PRO-T lymphocyte clones into TCR alpha,beta/T3+ and TCR gamma,delta/T3+ cells.
PRO-T lymphocyte clones, which have the T cell receptor (TCR) alpha, beta, gamma and delta genes in germline configuration and heterogeneous T cell precursors freshly isolated from bone marrow of athymic nude mice, gave rise to single positive L3T4+ TCR alpha,beta+ and double negative (L3T4-LyT2-) TCR alpha,beta+ or TCR gamma,delta+ cells, but not to any cells expressing LyT2, when co-cultured with the thymic epithelial clone ET. The T cell progenitors were able to develop into cells expressing LyT2 only when cocultured with heterogeneous thymic epithelial cell preparations. The progeny of the induced PRO-T clones included cells bearing V beta 8, V beta 17 and V gamma 3 gene family products. The presence of cells expressing a TCR gamma, delta/T3 receptor complex in the cultures was also documented by the expression of RNA transcripts from the TCR delta and TCR gamma genes by induced PRO-T cells. The TCR/T3+ cells generated in the cultures expressed functionally competent T cell receptor complexes. Our results show that: (i) the same PRO-T clone can give rise to all major subsets of thymocytes upon interaction with the appropriate thymic epithelial cells; (ii) both TCR alpha,beta+ and TCR gamma,delta+ cells may originate from a common T cell progenitor; (iii) L3T4+ TCR alpha, beta+ and L3T4-LyT2- TCR alpha,beta+ cells do not necessarily pass through a L3T4+LyT2+ intermediate stage of development; and (iv) different types of thymic epithelial cells play an essential role in the differentiation of PRO-T cells into either L3T4+ TCR alpha,beta+ L3T4-LyT2- TCR alpha,beta+ or L3T4+LyT2+ and LyT2+ TCR alpha, beta+ cells in vitro. Finally, we have attempted to integrate our results and those of others in a suggested model of T cell development within the thymus.
Palacios
R
R
Basel Institute for Immunology, Switzerland.
Studer
S
S
Samaridis
J
J
Pelkonen
J
J
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002999:Clone Cells; D004848:Epithelium / Q000276:immunology; D015321:Gene Rearrangement; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D051379:Mice; D008819:Mice, Nude; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell