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

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    Antigen-Presenting Cells
    Interleukin-12
    Helper-Inducer T-Lymphocytes
    Interleukin-2
    Clone Cells
    Interleukin-12 Receptors
    Population
    T-Lymphocytes
    Biological Assay
    Up-Regulation
    Binding Sites

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

    Cite this

    Maruo, S., Toyo-Oka, K., Ohora, M., Tai, X. G., Iwata, H., Takenaka, H., ... 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.

    IL-12 produced by antigen-presenting cells induces IL-2-independent proliferation of T helper cell clones. / Maruo, S.; Toyo-Oka, K.; Ohora, Masatsugu; Tai, X. G.; Iwata, H.; Takenaka, H.; Yamada, S.; Ono, S.; Hamaoka, T.; Kobayashi, M.; Wysocka, M.; Trinchieri, G.; Fujiwara, H.

    In: Journal of Immunology, Vol. 156, No. 5, 05.03.1996, p. 1748-1755.

    Research output: Contribution to journalArticle

    Maruo, S, Toyo-Oka, K, Ohora, M, Tai, XG, 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, vol. 156, no. 5, pp. 1748-1755.
    Maruo S, Toyo-Oka K, Ohora M, Tai XG, Iwata H, Takenaka H et al. IL-12 produced by antigen-presenting cells induces IL-2-independent proliferation of T helper cell clones. Journal of Immunology. 1996 Mar 5;156(5):1748-1755.
    Maruo, S. ; Toyo-Oka, K. ; Ohora, Masatsugu ; Tai, X. G. ; Iwata, H. ; Takenaka, H. ; Yamada, S. ; Ono, S. ; Hamaoka, T. ; Kobayashi, M. ; Wysocka, M. ; Trinchieri, G. ; Fujiwara, H. / IL-12 produced by antigen-presenting cells induces IL-2-independent proliferation of T helper cell clones. In: Journal of Immunology. 1996 ; Vol. 156, No. 5. pp. 1748-1755.
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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.",
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    AU - Maruo, S.

    AU - Toyo-Oka, K.

    AU - Ohora, Masatsugu

    AU - Tai, X. G.

    AU - Iwata, H.

    AU - Takenaka, H.

    AU - Yamada, S.

    AU - Ono, S.

    AU - Hamaoka, T.

    AU - Kobayashi, M.

    AU - Wysocka, M.

    AU - Trinchieri, G.

    AU - Fujiwara, H.

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