+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Interleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones



Interleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones



Journal of Experimental Medicine 179(4): 1273-1283



Interleukin 12 (IL-12) facilitates the generation of a T helper type 1 (Th1) response, with high interferon gamma (IFN-gamma) production, while inhibiting the generation of IL-4-producing Th2 cells in polyclonal cultures of both human and murine T cells and in vivo in the mouse. In this study, we analyzed the effect of IL-12, present during cloning of human T cells, on the cytokine profile of the clones. The culture system used allows growth of clones from virtually every T cell, and thus excludes the possibility that selection of precommitted Th cell precursors plays a role in determining characteristics of the clones. IL-12 present during the cloning procedures endowed both CD4+ and CD8+ clones with the ability to produce IFN-gamma at levels severalfold higher than those observed in clones generated in the absence of IL-12. This priming was stable because the high levels of IFN-gamma production were maintained when the clones were cultured in the absence of IL-12 for 11 d. The CD4+ and some of the CD8+ clones produced variable amounts of IL-4. Unlike IFN-gamma, IL-4 production was not significantly different in clones generated in the presence or absence of IL-12. These data suggest that IL-12 primes the clone progenitors, inducing their differentiation to high IFN-gamma-producing clones. The suppression of IL-4-producing cells observed in polyclonally generated T cells in vivo and in vitro in the presence of IL-12 is not observed in this clonal model, suggesting that the suppression depends more on positive selection of non-IL-4-producing cells than on differentiation of individual clones. However, antigen-specific established Th2 clones that were unable to produce IFN-gamma with any other inducer did produce IFN-gamma at low but significant levels when stimulated with IL-12 in combination with specific antigen or insoluble anti-CD3 antibodies. This induction of IFN-gamma gene expression was transient, because culture of the established clones with IL-12 for up to 1 wk did not convert them into IFN-gamma producers when stimulated in the absence of IL-12. These results suggest that Th clones respond to IL-12 treatment either with a stable priming for IFN-gamma production or with only a transient low level expression of the IFN-gamma gene, depending on their stage of differentiation.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 068670083

Download citation: RISBibTeXText

PMID: 7908322

DOI: 10.1084/jem.179.4.1273


Related references

Interleukin 12 induces stable priming for interferon gamma (Ifn-gamma) production during differentiation of human T helper (Th) cells and transient Ifn-gamma production in established Th2 cell clones. Journal of Experimental Medicine 179(4): 1273-1283, 1994

Interleukin 12 induces stable priming for interferon gamma production during differentiation of human T helper cells and transient IFN-gamma production in established Th2 cell clones. Journal of Experimental Medicine 179(4): 1273-1283, 1994

Interferon-gamma-inducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin-12 for interferon-gamma production. European Journal of Immunology 26(7): 1647-1651, 1996

Human interleukin-12 upregulates proliferation and interferon-gamma production by parasite antigen-stimulated Th cell clones and gamma/delta T cells of cattle. Annals of the new York Academy of Sciences 795: 321-324, 1996

Priming for high interferon-gamma production induced by interleukin-12 in both CD4+ and CD8+ T cell clones from HIV-infected patients. Journal of Clinical Investigation 96(3): 1677-1682, 1995

Interleukin-18 induces interferon-gamma production through NF-kappaB and NFAT activation in murine T helper type 1 cells. Cellular Immunology 196(1): 41-50, 1999

Production of interferon gamma and tumor necrosis factor alpha by human t cell clones expressing different forms of the gamma delta receptor. Immunology 71(4): 486-492, 1990

Interleukin-12 primes human CD4 and CD8 T cell clones for high production of both interferon-gamma and interleukin-10. Journal of Experimental Medicine 183(6): 2559-2569, 1996

B7 and interleukin 12 cooperate for proliferation and interferon gamma production by mouse T helper clones that are unresponsive to B7 costimulation. Journal of Experimental Medicine 180(1): 223-231, 1994

Histamine affects interleukin-4, interleukin-5, and interferon-gamma production by human T cell clones from the airways and blood. American Journal of Respiratory Cell and Molecular Biology 18(5): 721-730, 1998

Inhibitory effects of histamine on interleukin 2 and gamma interferon production by different human t helper cell subsets. Scandinavian Journal of Immunology 28(6): 727-734, 1988

Production of ige by purified epstein barr virus ebv infected human b cells is induced by interleukin 4 il 4 and suppressed by interferon gamma ifn gamma. Clinical Research 37(2): 515A, 1989

Interleukin 12 acts directly on CD4+ T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming. Proceedings of the National Academy of Sciences of the United States of America 90(21): 10188-10192, 1993

Interferon-gamma, interleukin-4 and interleukin-10 production by T helper cells reveals intact Th1 and regulatory TR1 cell activation and a delay of the Th2 cell response in equine neonates and foals. Veterinary Research 41(4): 47, 2010

Human T-cell clones against Toxoplasma gondii: production of interferon-gamma, interleukin-2, and strain cross-reactivity. Parasitology Research 77(5): 379-385, 1991