T cell development in insulin-like growth factor-II transgenic mice.
Growth hormone and insulin-like growth factor-I (IGF-I) have been demonstrated to play a role in T and B cell development. We studied the effects of IGF-II on T cell development in two transgenic mouse lines that overexpress human IGF-II under the control of the H2Kb promoter. The thymuses of 1-wk-old mice of two transgenic lines (5'-35 and 5'-74) contained 36 and 68%, respectively, more thymocytes than controls. Between 1 and 4 wk of age, the overexpression of IGF-II also resulted in a 2 to 2.5 times stronger increase in thymic cellularity. As in control mice, the number of thymocytes declined after 4 wk of age, and at 15 wk it was no longer significantly different from controls. Flowcytometric analysis indicated that at 2 and 4 wk of age, the increased thymic cellularity was associated with an increased number of early (CD4- CD8- or CD4- CD8dim), intermediate (CD4+CD8+), and mature thymocytes (CD3++CD4+CD8- or CD3++CD4-CD8+). However, the increase in the number of CD4+CD8- thymocytes was larger than the increase in the number of CD4-CD8+ thymocytes. As a consequence, CD4+ T cells mainly contributed to the increase in the number of T cells in spleen. These T cells showed a mature phenotype since they expressed CD3 and were negative for heat-stable antigen, a marker for immature T cells. These data indicate that overexpression of IGF-II increases thymic cellularity and stimulates the generation of phenotypically normal T cells with a preference to CD4+ cells.
Kooijman
R
R
Department of Immunology, University Hospital for Children and Youths, Utrecht, The Netherlands.
van Buul-Offers
S C
SC
Scholtens
L E
LE
Schuurman
H J
HJ
Van den Brande
L J
LJ
Zegers
B J
BJ
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D007335:Insulin-Like Growth Factor II / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology*
D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II