Impaired thymopoiesis in interleukin-7 receptor transgenic mice is not corrected by Bcl-2.
Murine thymocytes down-regulate IL-7 responsiveness following beta-selection and reacquire sensitivity after positive selection. To assess the potential consequences of IL-7 signaling during this phase of development, transgenic IL-7 receptor alpha (IL-7Ralpha) mice were evaluated for IL-7 responsiveness as gauged by STAT-5 phosphorylation. Transgenic IL-7Ralpha expression increased the percentage of thymocytes responsive to IL-7 yet resulted in a decrease in total thymic cellularity. Aberrant thymocyte development in transgenic mice was first manifested by a reduction of DN3 thymocytes that correlated with lower Bcl-2 expression. Surprisingly, transgenic restoration of Bcl-2 expression did not correct thymic hypocellularity induced by IL-7Ralpha overexpression. These findings demonstrate that failure to appropriately downregulate IL-7Ralpha expression interferes with thymocyte development past the pro-T stage resulting in significantly lower levels of mature thymocytes.
Van de Wiele
C Justin
CJ
University of Oklahoma College of Medicine, Department of Surgery, 4502 E. 41st Street, Tulsa, OK 74135, USA.
Marino
Julie H
JH
Tan
Chibing
C
Kneale
Hilary A
HA
Weber
John
J
Morelli
John N
JN
Davis
Brenda K
BK
Taylor
Ashlee A
AA
Teague
T Kent
TK
D000818:Animals; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D053699:Interleukin-7 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism*; D038041:Lymphopoiesis / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology / Q000276:immunology
D018076:DNA, Complementary; D053699:Interleukin-7 Receptor alpha Subunit; D019253:Proto-Oncogene Proteins c-bcl-2