Interleukin-12: A Cytokine at the Interface of Inflammation and Immunity

TH1 and TH2 Cells: Different Patterns of Lymphokine Secretion Lead to Different Functional Properties

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An endotoxin-induced serum factor that causes necrosis of tumors

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Current Protocols in Immunology

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Development of T _H 1 CD4 ⁺ T Cells Through IL-12 Produced by <i>Listeria</i> -Induced Macrophages

Hsieh, C.-S., Macatonia, S. E., Tripp, C. S., Wolf, S. F., O'Garra, A., & Murphy, K. M. (1993) · Science · doi:10.1126/science.8097338 · Cited by 3,134 · see citing works

Biology of Natural Killer Cells

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Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones.

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Cloning of a new cytokine that induces IFN-γ production by T cells

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Interleukin-12: A Proinflammatory Cytokine with Immunoregulatory Functions that Bridge Innate Resistance and Antigen-Specific Adaptive Immunity

Trinchieri, G. (1995) · Annual Review of Immunology · doi:10.1146/annurev.iy.13.040195.001343 · Cited by 2,427 · see citing works

Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation.

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Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity.

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Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes.

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Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells.

Manetti, R., Parronchi, P., Giudizi, M. G., Piccinni, M., Maggi, E., Trinchieri, G., & Romagnani, S. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.177.4.1199 · Cited by 1,666 · see citing works

Gp130 and the interleukin-6 family of cytokines.

Taga, T., & Kishimoto, T. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.797 · Cited by 1,603 · see citing works

Acquisition of lymphokine-producing phenotype by CD4+ T cells

Seder, R. A., & Paul, W. E. (1994) · Annual Review of Immunology · doi:10.1146/annurev.iy.12.040194.003223 · Cited by 1,557 · see citing works

Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells.

Macatonia, S. E., Hosken, N. A., Litton, M. J., Vieira, P., Hsieh, C., Culpepper, J., Wysocka, M., Trinchieri, G., MURPHY, K. M. M., & O’Garra, A. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.10.5071 · Cited by 1,524 · see citing works

CpG motifs present in bacteria DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma.

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A TH1→TH2 switch is a critical step in the etiology of HIV infection

Clerici, M. S., & Shearer, G. M. (1993) · Immunology Today · doi:10.1016/0167-5699(93)90208-3 · Cited by 1,399 · see citing works

Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130

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Differentiation and proliferation of hematopoietic stem cells

Ogawa, M. (1993) · Blood · doi:10.1182/blood.v81.11.2844.2844 · Cited by 1,395 · see citing works

Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma-production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells.

D’Andrea, A., Aste-Amézaga, M., Valiante, N. M., Ma, X., Kubin, M. Z., & Trinchieri, G. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.178.3.1041 · Cited by 1,367 · see citing works

MOUSE CD1-SPECIFIC NK1 T CELLS: Development, Specificity, and Function

Bendelac, A. S., Rivera, M. N., Park, S., et al. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.535 · Cited by 1,339 · see citing works

Antibodies to interleukin 12 abrogate established experimental colitis in mice.

Neurath, M., Fuss, I. J., Kelsall, B. L., Stuber, E. R., & Strober, W. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.182.5.1281 · Cited by 1,334 · see citing works

IL‐4 directs the development of Th2‐like helper effectors

Swain, S. L., Weinberg, A. D., English, M., & Huston, G. (1990) · The Journal of Immunology · doi:10.4049/jimmunol.145.11.3796 · Cited by 1,254 · see citing works

Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice

Kaplan, M. H., Sun, Y.-L., Hoey, T., & Grusby, M. J. (1996) · Nature · doi:10.1038/382174a0 · Cited by 1,240 · see citing works

Macrophage deactivation by interleukin 10.

Bogdan, C., Yoram Vodovotz, B., & Nathan, C. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.174.6.1549 · Cited by 1,236 · see citing works

Caspase-1 processes IFN-γ-inducing factor and regulates LPS-induced IFN- γ production

Ghayur, T., Banerjee, S., Hugunin, M., Butler, D., Herzog, L., Carter, A. B., Quintal, L. J., Sekut, L., Talanian, R. V., Paskind, M. P., et al. (1997) · Nature · doi:10.1038/386619a0 · Cited by 1,204 · see citing works

Antitumor and antimetastatic activity of interleukin 12 against murine tumors.

Brunda, M. J., Luistro, L. L., Warrier, R. R., Wright, R. B., Hubbard, B. R., Murphy, M. E., Wolf, S. F., & Gately, M. K. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.178.4.1223 · Cited by 1,197 · see citing works

Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells

Thierfelder, W. E., van Deursen, J. M., Yamamoto, K., Tripp, R. A., Sarawar, S. R., Carson, R. T., Sangster, M. Y., Vignali, D. A. A., Doherty, P. C., Grosveld, G. C., et al. (1996) · Nature · doi:10.1038/382171a0 · Cited by 1,181 · see citing works

Activation of Interferon-γ Inducing Factor Mediated by Interleukin-1β Converting Enzyme

Gu, Y., Kuida, K., Tsutsui, H., Ku, G., Hsiao, K., Fleming, M. A., Hayashi, N., Higashino, K., Okamura, H., Nakanishi, K., et al. (1997) · Science · doi:10.1126/science.275.5297.206 · Cited by 1,159 · see citing works

Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells.

D’Andrea, A., Rengaraju, M., Valiante, N. M., Chehimi, J., Kubin, M. Z., Aste-Amézaga, M., Chan, S. H., Kobayashi, M., Young, D., & Nickbarg, E. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.176.5.1387 · Cited by 1,143 · see citing works

An alternative pathway of T-cell activation: A functional role for the 50 kd T11 sheep erythrocyte receptor protein

Meuer, S. C., Hussey, R. E., Fabbi, M., Fox, D. A., Acuto, O., Fitzgerald, K. A., Hodgdon, J. C., Protentis, J. P., Schlossman, S. F., & Reinherz, E. L. (1984) · Cell · doi:10.1016/0092-8674(84)90039-4 · Cited by 1,113 · see citing works

Immunostimulatory DNA Sequences Necessary for Effective Intradermal Gene Immunization

Sato, Y., Roman, M., Tighe, H., Lee, D. J., Corr, M., Nguyen, M., Silverman, G. J., Lotz, M., Carson, D. A., & Raz, E. (1996) · Science · doi:10.1126/science.273.5273.352 · Cited by 1,052 · see citing works

Interleukin-12: a cytokine produced by antigen-presenting cells with immunoregulatory functions in the generation of T-helper cells type 1 and cytotoxic lymphocytes

Trinchieri, G. (1994) · Blood · doi:10.1182/blood.v84.12.4008.bloodjournal84124008 · Cited by 1,045 · see citing works

THE TREATMENT OF MALIGNAT TUMORS BY REPEATED INOCULATIONS OF ERYSIPELAS

COLEY, W. B. (1893) · The American Journal of the Medical Sciences · doi:10.1097/00000441-189305000-00001 · Cited by 994 · see citing works

The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice.

Seder, R. A., Paul, W. E., Davis, M. M., & Groth, B. F. D. S. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.176.4.1091 · Cited by 994 · see citing works

IL-12-Deficient Mice Are Defective in IFNγ Production and Type 1 Cytokine Responses

Magram, J., Connaughton, S. E., Warrier, R. R., Carvajal, D. M., Wu, C. Y., Ferrante, J., Stewart, C. L., Sarmiento, U. M., Faherty, D. A., & Gately, M. K. (1996) · Immunity · doi:10.1016/s1074-7613(00)80413-6 · Cited by 989 · see citing works

Recognition of a lipid antigen by CD1-restricted αβ+ T cells

Beckman, E. M., Porcelli, S. A., Morita, C. T., Behar, S. M., Furlong, S. T., & Brenner, M. B. (1994) · Nature · doi:10.1038/372691a0 · Cited by 977 · see citing works

Interleukin 12 acts directly on CD4+ T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming.

Seder, R. A., Gazzinelli, R. T., Sher, A., & Paul, W. E. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.21.10188 · Cited by 976 · see citing works

Regulation of the Interleukin (IL)-12R β2 Subunit Expression in Developing T Helper 1 (Th1) and Th2 Cells

Szabo, S. J., Dighe, A. S., Gubler, U., & MURPHY, K. M. M. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.5.817 · Cited by 973 · see citing works

Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cells and synergy with other inducers.

Chan, S. H., PERUSSIA, B., Gupta, J. W., Kobayashi, M., Pospísil, M., Young, H. A., Wolf, S. F., Young, D., Clark, S., & Trinchieri, G. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.173.4.869 · Cited by 962 · see citing works

Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells.

Le Gros, G., Ben-Sasson, S. Z., Seder, R., Finkelman, F. D., & Paul, W. E. (1990) · The Journal of experimental medicine · doi:10.1084/jem.172.3.921 · Cited by 954 · see citing works

Interleukin-12 and its role in the generation of TH1 cells.

Trinchieri, G. (1993) · Immunology today (Amsterdam. Regular ed.) · doi:10.1016/0167-5699(93)90230-i · Cited by 931 · see citing works

In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-γ and TNF-α

Gazzinelli, R. T., Wysocka, M., Hieny, S. E., Scharton‐Kersten, T., Cheever, A. W., Kühn, R., Müller, W., Trinchieri, G., & Sher, A. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.2.798 · Cited by 928 · see citing works

High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10.

Koch, F., Stanzl, U., Jennewein, P., Janke, K., Heufler, C., Kämpgen, E., Romani, N., & Schuler, G. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.2.741 · Cited by 928 · see citing works

Maturation Stages of Mouse Dendritic Cells in Growth Factor–dependent Long-Term Cultures

Winzler, C., Rovere, P. Q., Rescigno, M., Granucci, F., Penna, G., Adorini, L., Zimmermann, V. S., Davoust, J. M., & Ricciardi‐Castagnoli, P. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.2.317 · Cited by 848 · see citing works

Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells

Wolf, S. F., Temple, P. A., Kobayashi, M., Young, D. V., Dicig, M., Lowe, L. D., Dzialo, R., Fitz, L. J., Ferenz, C. R., & Hewick, R. M. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.146.9.3074 · Cited by 845 · see citing works

Interleukin 12 is required for the T-lymphocyte-independent induction of interferon gamma by an intracellular parasite and induces resistance in T-cell-deficient hosts.

Gazzinelli, R. T., Hieny, S. E., Wynn, T. A., Wolf, S., & Sher, A. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.13.6115 · Cited by 835 · see citing works

CD40 Ligand Gene Defects Responsible for X-Linked Hyper-IgM Syndrome

Allen, R. C., Armitage, R. J., Conley, M. E., Rosenblatt, H. M., Jenkins, N. A., Copeland, N. G., Bedell, M. A., Edelhoff, S., Distèche, C. M., Simoneaux, D. K., et al. (1993) · Science · doi:10.1126/science.7679801 · Cited by 829 · see citing works

Recombinant IL-12 administration induces tumor regression in association with IFN- <i>gamma</i> production.

Nastala, C. L., Edington, H. D., McKinney, T. G., Tahara, H., Nalesnik, M. A., Brunda, M. J., Gately, M. K., Wolf, S. F., Schreiber, R. D., Storkus, W. J., et al. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.153.4.1697 · Cited by 780 · see citing works

Induction of TH1 and TH2 responses: a key role for the ‘natural’ immune response?

Romagnani, S. (1992) · Immunology Today · doi:10.1016/0167-5699(92)90083-j · Cited by 780 · see citing works

Interleukin 12 and tumor necrosis factor alpha are costimulators of interferon gamma production by natural killer cells in severe combined immunodeficiency mice with listeriosis, and interleukin 10 is a physiologic antagonist.

Tripp, C. S., Wolf, S. F., & Unanue, E. R. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.8.3725 · Cited by 768 · see citing works

Selective Expression of an Interleukin-12 Receptor Component by Human T Helper 1 Cells

Rogge, L., Barberis-Maino, L., Biffi, M., Passini, N., Presky, D. H., Gubler, U., & Sinigaglia, F. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.5.825 · Cited by 766 · see citing works

Recombinant interleukin 12 cures mice infected with Leishmania major.

Heinzel, F. P., Schoenhaut, D. S., Rerko, R. M., Rosser, L. E., & Gately, M. K. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.177.5.1505 · Cited by 761 · see citing works

Parasite-induced IL-12 stimulates early IFN- gamma synthesis and resistance during acute infection with Toxoplasma gondii .

Gazzinelli, R. T., Wysocka, M., Hayashi, S., Denkers, E., Hieny, S. E., Caspar, P., Trinchieri, G., & Sher, A. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.153.6.2533 · Cited by 729 · see citing works

Inhibition of Angiogenesis In Vivo by Interleukin 12

Voest, E. E., Kenyon, B. M., OʼReilly, M., Truitt, G. A., D’Amato, R. J., & Folkman, J. (1995) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/87.8.581 · Cited by 722 · see citing works

Resolution of cutaneous leishmaniasis: interleukin 12 initiates a protective T helper type 1 immune response.

Sypek, J. P., Chung, C. L., Mayor, S. E., Subramanyam, J. M., Goldman, S. J., Sieburth, D., Wolf, S. F., & Schaub, R. G. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.177.6.1797 · Cited by 721 · see citing works

IGIF Does Not Drive Th1 Development but Synergizes with IL-12 for Interferon-γ Production and Activates IRAK and NFκB

Robinson, D. S., Shibuya, K., Mui, A., Zonin, F., Murphy, E., Sana, T., Hartley, S. B., Menon, S., KASTELEIN, R. A., Bazán, F., et al. (1997) · Immunity · doi:10.1016/s1074-7613(00)80378-7 · Cited by 720 · see citing works

Interleukin 12 (IL-12) Is Crucial to the Development of Protective Immunity in Mice Intravenously Infected with Mycobacterium tuberculosis

Cooper, A. M., Magram, J., Ferrante, J., & Orme, I. M. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.1.39 · Cited by 715 · see citing works

CD40 ligand mutations in X-linked immunodeficiency with hyper-IgM

Santo, J. P. D., Bonnefoy, J., Gauchatt, J. F., Fischer, A., & Basile, G. D. S. (1993) · Nature · doi:10.1038/361541a0 · Cited by 702 · see citing works

Interleukin‐12 is produced by dendritic cells and mediates T helper 1 development as well as interferon‐γ production by T helper 1 cells

Heufler, C., Koch, F., Stanzl, U., Topar, G., Wysocka, M., Trinchieri, G., Enk, A., Steinman, R. M., Romani, N., & Schuler, G. (1996) · European Journal of Immunology · doi:10.1002/eji.1830260323 · Cited by 700 · see citing works

Purified protein derivative of Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with stable and opposite (type 1 T helper or type 2 T helper) profile of cytokine production.

Prete, G., Carli, M., Mastromauro, C., Biagiotti, R., Macchia, D., Falagiani, P., Ricci, M., & Romagnani, S. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115300 · Cited by 694 · see citing works

The Th1–Th2 hypothesis of HIV infection: new insights

Clerici, M. S., & Shearer, G. M. (1994) · Immunology Today · doi:10.1016/0167-5699(94)90220-8 · Cited by 693 · see citing works

A functional interleukin 12 receptor complex is composed of two β-type cytokine receptor subunits

Presky, D. H., Yang, H., Minetti, L. J., Chua, A. O., Nabavi, N., Wu, C. Y., Gately, M. K., & Gubler, U. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.14002 · Cited by 689 · see citing works

Cytokine-induced differentiation of precursor mouse CD8+ T cells into cytotoxic CD8+ T cells secreting Th1 or Th2 cytokines

Sad, S., Marcotte, R., & Mosmann, T. R. (1995) · Immunity · doi:10.1016/1074-7613(95)90051-9 · Cited by 685 · see citing works

Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4.

Jacobson, N. G., Szabo, S. J., Weber-Nordt, R., Zhong, Z.-H., Schreiber, R. D., Darnell, J. E., Jr., & MURPHY, K. M. M. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.5.1755 · Cited by 673 · see citing works

Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells.

STERN, A. S., Podlaski, F., Hulmes, J. D., Pan, Y.-C. E., Quinn, P. M., Wolitzky, A. G., Familletti, P. C., Stremlo, D. L., Truitt, T., & Chizzonite, R. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.17.6808 · Cited by 670 · see citing works

Prostaglandin-E2 is a potent inhibitor of human interleukin 12 production.

Kraan, T. C. T. M. V. D. P., Boeije, L. C. M., Smeenk, R. J. T., Wijdenes, J., & Aarden, L. A. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.2.775 · Cited by 665 · see citing works

Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFNγ receptors

Dighe, A. S., Richards, E., Old, L. J., & Schreiber, R. D. (1994) · Immunity · doi:10.1016/1074-7613(94)90087-6 · Cited by 663 · see citing works

Differential production of interferon-γ and interleukin-4 in response to Th1- and Th2-stimulating pathogens by γδ T cells in vivo

Ferrick, D. A., Schrenzel, M. D., Mulvania, T., Hsieh, B., Ferlin, W. G., & Lepper, H. (1995) · Nature · doi:10.1038/373255a0 · Cited by 662 · see citing works

Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10

de Waal Malefyt, R., Figdor, C. G., Huijbens, R., Mohan-Peterson, S., Bennett, B., Culpepper, J., Dang, W., Zurawski, G., & de Vries, J. E. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.11.6370 · Cited by 648 · see citing works

The interleukin 12 p40 gene promoter is primed by interferon gamma in monocytic cells.

Ma, X., Chow, J. M., Gri, G., Carra, G., Gerosa, F., Wolf, S. F., Dzialo, R., & Trinchieri, G. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.1.147 · Cited by 648 · see citing works

Immunodeficiency and Chronic Myelogenous Leukemia-like Syndrome in Mice with a Targeted Mutation of the ICSBP Gene

Holtschke, T., Löhler, J., Kanno, Y., Fehr, T., Giese, N., Rosenbauer, F., Lou, J., Knobeloch, K.-P., Gabriele, L., Waring, J. F., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81348-3 · Cited by 644 · see citing works

LIFRβ and gp130 as Heterodimerizing Signal Transducers of the Tripartite CNTF Receptor

Davis, S. H., Aldrich, T. H., Stahl, N., Li, P., Taga, T., Kishimoto, T., Ip, N. Y., & Yancopoulos, G. D. (1993) · Science · doi:10.1126/science.8390097 · Cited by 634 · see citing works

Crystal Structure of Mouse CD1: An MHC-Like Fold with a Large Hydrophobic Binding Groove

Zeng, Z.-H., Castaño, A. R., Segelke, B. W., Stura, E. A., Peterson, P. A., & Wilson, I. A. (1997) · Science · doi:10.1126/science.277.5324.339 · Cited by 631 · see citing works

Cloning of the cDNA for human IFN-γ-inducing factor, expression in Escherichia coli, and studies on the biologic activities of the protein

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Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation, and Th2 cytokine expression in mice.

Gavett, S. H., O’Hearn, D. J., Li, X., Huang, S. K., Finkelman, F. D., & Wills-Karp, M. A. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.182.5.1527 · Cited by 618 · see citing works

Natural killer cells are a source of interferon gamma that drives differentiation of CD4+ T cell subsets and induces early resistance to Leishmania major in mice.

Scharton, T. M., & Scott, P. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.178.2.567 · Cited by 613 · see citing works

Response of resting human peripheral blood natural killer cells to interleukin 2.

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