Thymic hyperplasia in transgenic mice caused by immortal epithelial cells expressing c-kit ligand.
To dissect mechanisms that co-ordinate specific events in thymopoiesis we have characterized alterations in thymic structure and function caused by expression of a transgene. This gene encodes SV40Tag and is specifically expressed in a subset of thymic epithelial (TE) cells around birth. As a result the number of immortal TE cells increases, thymic mass increases (up to 3 g), and thymopoiesis is expanded. The latter is reflected by a approximately 100-fold increase of the major thymocyte subsets and increased peripheral T cell counts. Grossly hyperplastic thymi retain many but not all morphological features of a normal thymus. Also in grafts, SV40Tag+ TE cells steer expansion (up to 8 g) and organize a tissue with mainly cortex-like features that includes mainly SV40Tag+ TE cells, thymocytes, and macrophages. To investigate expression of specialized gene functions in the immortal TE cells, a cell line was derived. The Epi-A1 cell line expresses the genes for major histocompatibility complex class I and II, Thy-1, interleukin (IL)-6, IL-7, macrophage-colony-stimulating factor, and transforming growth factor-beta 3. Most importantly, Epi-A1 cells also express the IL-4 receptor and the c-kit ligand (KL), a factor that, in concert with commitment factors, channels progenitors into hemopoietic lineages. The expression of low constitutive levels of KL mRNA does not require IL-4, but KL mRNA levels are increased dramatically in response to IL-4. Since constitutive expression of KL mRNA in vivo is restricted to a small subset of TE cells in the thymus, our findings reveal a novel specific interaction between thymocytes and a specialized subset of TE cells.
Moll
J
J
Department of Biotechnology, Ciba-Geigy Ltd., Freiburg.
Eibel
H
H
Schmid
P
P
Sansig
G
G
Botteri
F
F
Palacios
R
R
Van der Putten
H
H
D000367:Age Factors; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000032:analysis; D004848:Epithelium / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D013007:Growth Hormone-Releasing Hormone / Q000096:biosynthesis; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000494:pharmacology; D007378:Interleukins / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019009:Proto-Oncogene Proteins c-kit; D012313:RNA / Q000032:analysis; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D013952:Thymus Hyperplasia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000502:physiology
D003115:Colony-Stimulating Factors; D007378:Interleukins; D015345:Oligonucleotide Probes; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D012313:RNA; D013007:Growth Hormone-Releasing Hormone; D019009:Proto-Oncogene Proteins c-kit