IFN-gamma reverses IL-4 inhibition of fetal thymus growth in organ culture.
IL-4 is known to inhibit the growth and differentiation of 14-day-old fetal mouse thymus in organ culture. Here we report that IFN-gamma reverses this IL-4-mediated growth inhibition. Thymus lobes from 14-day-old fetuses were cultured for 12 days in medium containing 100 IU/ml rIL-4 either in the absence or presence of rIFN-gamma (100 to 1000 IU/ml). After culture, the cell yields and the absolute numbers and frequencies of the major subpopulations according the coordinate expression of CD4 and CD8 were estimated. IL-4 treatment alone was found to result in a seven-fold decrease in cell yield and an almost complete absence of the CD4+CD8+ subpopulation. Addition of IFN-gamma reversed IL-4-mediated inhibition in a dose-dependent fashion, with an optimal dose ranging from 200 to 500 IU/ml. IFN-gamma exerted this effect only when added within the first 48 h of initiating the culture. The specificity of the reversal effect was ascertained by neutralization of the effect by a neutralizing anti-IFN-gamma mAb and by lack of activity of human IFN-gamma. In the absence of IL-4, IFN-gamma had a growth-promoting effect as evident from a threefold increase in cell numbers.
Plum
J
J
Department of Bacteriology, Virology and Immunology, University Hospital of Gent, Belgium.
De Smedt
M
M
Billiau
A
A
Heremans
H
H
Leclercq
G
G
Tison
B
B
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors*; D051379:Mice; D008807:Mice, Inbred BALB C; D009924:Organ Culture Techniques; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011994:Recombinant Proteins; D016176:T-Lymphocyte Subsets / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000254:growth & development*
D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma