The Journal of Immunology, Vol 156, Issue 7 2413-2422, Copyright © 1996 by American Association of Immunologists

ARTICLES

High-dose IL-2 and IL-15 enhance the in vitro priming of naive CD4+ T cells for IFN-gamma but have differential effects on priming for IL-4

RA Seder
Lymphokine Regualtion Unit, Labortory of Clinical Investigation, National Insitute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.

Cytokines play an important role for the in vitro differentiation of naive CD4+ T cells into IL-4- or IFN-gamma-producing cells. The presence of both IL-4 and IL-2 is required to prime cells for IL-4 in vitro. Using purified CD4+/LECAM-1high T cells from TCR transgenic mice as naive responder cells, the role of IL-15 was studied to see if it functioned similarly to IL-2 with regard to IL-4 priming. Purified CD4+ T cells cultured in the presence of IL-4 and anti-IL-2 failed to prime cells for IL-4 production. Addition of IL-15 to these same cultures could not restore priming for IL-4, suggesting that IL-2 and IL-15 may have different functional properties during the in vitro differentiation of IL-4-producing cells. The role of IL-15 in priming for IFN-gamma was also examined. The addition of high doses of IL-15 to priming cultures resulted in a striking increase in the amount of IFN- gamma produced following restimulation. Similarly, addition of a relatively high dose of IL-2 also produced a significant enhancement of IFN-gamma production; however, as previously reported, the presence of IL-12 in priming cultures induced the greatest increase in IFN-gamma production, leaving it as the predominant controller of Th1 differentiation in physiologic situations. Finally, IL-15 was shown to increase proliferation of activated CD4+ T cell blasts but not of naive CD4+ T cells. Moreover, cultures containing both IL-12 and IL-15 showed greater proliferation than either cytokine alone, suggesting an additive effect between these cytokines.

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