Detection of a novel population of fetal thymocytes characterized by preferential emigration and a TCRgammadelta+ T cell fate after dioxin exposure.
T cell maturation into TCRalphabeta(+) or TCRgammadelta(+) cells from common immature CD4(-)CD8(-)(DN) precursors occurs in the thymus, and is controlled through ordered regulation of genes. The aryl hydrocarbon receptor (AHR), a latent cytoplasmic transcription factor, affects thymocyte maturation and differentiation at several stages, also including DN cells. We analyzed in murine fetal thymus organ cultures (FTOC) the outcome of AHR-signaling and found a higher frequency of DN TCRgammadelta(+) cells in the presence of the AHR-activating ligand TCDD. We detected a novel population of CD25(int/lo)CD44(hi) cells associated with preferential emigration and a TCRgammadelta(+) T cell fate of thymocytes. Sorted DN TCRgammadelta(+) emigrants could proliferate if IL-2 was available. Moreover, they suppressed the proliferation of co-cultivated, activated CD4(+) T cells. Gene expression profiles of purified DN emigrants from TCDD*FTOC revealed 295 modulated genes, 10% of which are genes of the immune system. For instance, RAG-1, TdT, and Gfi-1 were downregulated, yet genes indicative of mature thymocytes were upregulated. In conclusion, we have detected changes in the differentiation programme of fetal DN thymocytes after ligand-activation of the AHR. In particular, we observed a higher frequency of DN TCRgammadelta(+) cells with high emigration potential, and possible regulatory functions.
Majora
Marc
M
Institute for Environmental Medical Research (IUF) at the Heinrich-Heine University of Düsseldorf, Auf'm Hennekamp 50, 40225 Düsseldorf, Germany.
Frericks
Markus
M
Temchura
Vladimir
V
Reichmann
Gaby
G
Esser
Charlotte
C
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018960:Hyaluronan Receptors / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D012313:RNA / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis* / Q000276:immunology; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000276:immunology
D018960:Hyaluronan Receptors; D000072317:Polychlorinated Dibenzodioxins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018336:Receptors, Aryl Hydrocarbon; D012313:RNA