The Journal of Immunology, Vol 147, Issue 1 50-54, Copyright © 1991 by American Association of Immunologists

ARTICLES

IFN-gamma reverses IL-4 inhibition of fetal thymus growth in organ culture

J Plum, M De Smedt, A Billiau, H Heremans, G Leclercq and B Tison
Department of Bacteriology, Virology and Immunology, University Hospital of Gent, Belgium.

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.

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