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.
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.
Seder
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RA
Lymphokine Regualtion Unit, Labortory of Clinical Investigation, National Insitute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D003574:Cytochrome c Group / Q000235:genetics / Q000276:immunology; D004357:Drug Synergism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000008:administration & dosage; D019409:Interleukin-15; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D015847:Interleukin-4 / Q000096:biosynthesis*; D007378:Interleukins / Q000008:administration & dosage*; D019041:L-Selectin / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage; D018417:Th1 Cells / Q000276:immunology
D000941:Antigens; D003574:Cytochrome c Group; D019409:Interleukin-15; D007376:Interleukin-2; D007378:Interleukins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D019041:L-Selectin; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma