IL-12 produced by antigen-presenting cells induces IL-2-independent proliferation of T helper cell clones

S. Maruo, K. Toyo-Oka, Masatsugu Ohora, X. G. Tai, H. Iwata, H. Takenaka, S. Yamada, S. Ono, T. Hamaoka, M. Kobayashi, M. Wysocka, G. Trinchieri, H. Fujiwara

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    Abstract

    We investigated the role of IL-12 in proliferation of various Th cell clones (class II-alloreactive (4-86 and 4-55) and keyhole limpet hemocyanin + self I-E(k)-reactive (9-16)) following stimulation with Ag on APCs. These clones proliferated in response to stimulation with rIL-2, rIL-12, or Ag/APC. The proliferation induced by Ag/APC stimulation was not affected by anti-IL- 2 Ab but was markedly inhibited by anti-IL-12 Abs. Consistent with this finding was the absence of detectable IL-2 activity in culture supernatants 12 to 48 h after Ag/APC stimulation, and the detection of significant levels of IL-12 in an Ab-capture bioassay. IL-12 was produced within 12 h after Ag/APC stimulation, reaching a peak after 18 to 24 h. The production of IL- 12 in cultures of Th clones and APC contrasted with the production of IL-2 but not IL-12 upon allostimulation of primary T cells and the inhibition of their proliferation exclusively by anti-IL-2 Abs. Analysis of the expression of IL-12-binding sites on Th cells revealed low levels of IL-12 receptors in resting Th clones but high IL-12R levels 2 to 3 days after Ag/APC stimulation, declining gradually thereafter. The changes in IL-12R expression levels correlated closely with the IL-12 responsiveness of Th populations at various times after Ag/APC stimulation; Th populations obtained 3 and 10 days after Ag/APC stimulation exhibited very high and weak or marginal responsiveness to rIL-12, respectively, whereas the responses to rIL-2 were comparable in both Th populations. These results indicate that the Ag/APC- stimulated proliferation of terminally differentiated Th clones, in contrast to naive T cells, depends on the production of IL-12 by APC and on the simultaneous up-regulation of IL-12R on Th cells rather than on an IL-2 autocrine mechanism.

    Original languageEnglish
    Pages (from-to)1748-1755
    Number of pages8
    JournalJournal of Immunology
    Volume156
    Issue number5
    Publication statusPublished - Mar 5 1996

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

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  • Cite this

    Maruo, S., Toyo-Oka, K., Ohora, M., Tai, X. G., Iwata, H., Takenaka, H., Yamada, S., Ono, S., Hamaoka, T., Kobayashi, M., Wysocka, M., Trinchieri, G., & Fujiwara, H. (1996). IL-12 produced by antigen-presenting cells induces IL-2-independent proliferation of T helper cell clones. Journal of Immunology, 156(5), 1748-1755.