Effect of IL-7 on the growth of fetal thymocytes in culture.
The effects of IL-7 on the in vitro growth and differentiation of day 12 to 14 murine fetal thymocytes were examined in three culture systems. In single cell suspension cultures, IL-7 and IL-2 induced a DNA synthetic response in a short term (1 day) assay, but neither cytokine supported continued cell growth. In conventional fetal thymus organ cultures, the addition of exogenous IL-7 resulted in a twofold increase in cell number over that which normally develops in unsupplemented fetal thymus organ cultures during a 7-day period. The most striking effects of IL-7 were noted in lobe submersion cultures (LSC), a system in which thymocyte growth was totally dependent on the addition of exogenous cytokine. Cells proliferated for a period of approximately 2 wk in IL-7, and cell viability could be maintained even longer. A high percentage of cells recovered after 7 to 14 days from IL-7-supplemented LSC resembled the earliest detectable fetal thymocytes with regard to cell surface markers: they expressed Pgp-1, lacked CD4, CD8, and CD3 and many expressed the IL-2R. These results suggest that IL-7 promotes the growth of cells that occur early in the T cell lineage. Cell populations recovered from LSC supplemented with IL-7 and IL-2 exhibited differential expression of some surface markers, particularly CD3 and NK1.1. In addition, cells from LSC supplemented with IL-7 were found to proliferate upon subsequent exposure to IL-2, but cells from LSC containing exogenous IL-2 were no longer responsive to IL-7. These results imply that IL-7 and IL-2 may act at different stages of thymocyte differentiation. Together with previous observations of IL-7-specific mRNA expression in the thymus, this study provides evidence highly suggestive of a pivotal role for IL-7 in T cell development.
Watson
J D
JD
Department of Immunobiology, School of Medicine, Auckland University, New Zealand.
Morrissey
P J
PJ
Namen
A E
AE
Conlon
P J
PJ
Widmer
M B
MB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D002455:Cell Division; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000502:physiology; D005260:Female; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D015851:Interleukin-7; D007378:Interleukins / Q000276:immunology / Q000494:pharmacology*; D008212:Lymphocyte Depletion; D051379:Mice; D009924:Organ Culture Techniques; D010641:Phenotype; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000196:embryology* / Q000276:immunology / Q000502:physiology
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D015851:Interleukin-7; D007378:Interleukins; D003165:Complement System Proteins