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

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

DF Fiorentino, MW Bond and TR Mosmann
Department of Immunology, DNAX Research Institute, Palo Alto, California 94304.

A cytokine synthesis inhibitory factor (CSIF) is secreted by Th2 clones in response to Con A or antigen stimulation, but is absent in supernatants from Con A-induced Th1 clones. CSIF can inhibit the production of IL-2, IL-3, lymphotoxin (LT)/TNF, IFN-gamma, and granulocyte-macrophage CSF (GM-CSF) by Th1 cells responding to antigen and APC, but Th2 cytokine synthesis is not significantly affected. Transforming growth factor beta (TGF-beta) also inhibits IFN-gamma production, although less effectively than CSIF, whereas IL-2 and IL-4 partially antagonize the activity of CSIF. CSIF inhibition of cytokine synthesis is not complete, since early cytokine synthesis (before 8 h) is not significantly affected, whereas later synthesis is strongly inhibited. In the presence of CSIF, IFN-gamma mRNA levels are reduced slightly at 8, and strongly at 12 h after stimulation. Inhibition of cytokine expression by CSIF is not due to a general reduction in Th1 cell viability, since actin mRNA levels were not reduced, and proliferation of antigen-stimulated cells in response to IL-2, was unaffected. Biochemical characterization, mAbs, and recombinant or purified cytokines showed that CSIF is distinct from IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IFN-gamma, GM-CSF, TGF-beta, TNF, LT, and P40. The potential role of CSIF in crossregulation of Th1 and Th2 responses is discussed.
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Gerber, J. S., Mosser, D. M. (2001). Reversing Lipopolysaccharide Toxicity by Ligating the Macrophage Fc{{gamma}} Receptors. J. Immunol. 166: 6861-6868 [Abstract] [Full Text]
Kawamoto, S., Nitta, Y., Tashiro, F., Nakano, A., Yamato, E., Tahara, H., Tabayashi, K., Miyazaki, J.-i. (2001). Suppression of Th1 cell activation and prevention of autoimmune diabetes in NOD mice by local expression of viral IL-10. Int Immunol 13: 685-694 [Abstract] [Full Text]
Gonnella, P. A., Waldner, H. P., Weiner, H. L. (2001). B Cell-Deficient ({micro}MT) Mice Have Alterations in the Cytokine Microenvironment of the Gut-Associated Lymphoid Tissue (GALT) and a Defect in the Low Dose Mechanism of Oral Tolerance. J. Immunol. 166: 4456-4464 [Abstract] [Full Text]
Huang, D., Wang, J., Kivisakk, P., Rollins, B. J., Ransohoff, R. M. (2001). Absence of Monocyte Chemoattractant Protein 1 in Mice Leads to Decreased Local Macrophage Recruitment and Antigen-specific T Helper Cell Type 1 Immune Response in Experimental Autoimmune Encephalomyelitis. J. Exp. Med. 193: 713-726 [Abstract] [Full Text]
Bhattacharyya, S., Ghosh, S., Jhonson, P. L., Bhattacharya, S. K., Majumdar, S. (2001). Immunomodulatory Role of Interleukin-10 in Visceral Leishmaniasis: Defective Activation of Protein Kinase C-Mediated Signal Transduction Events. Infect. Immun. 69: 1499-1507 [Abstract] [Full Text]
Torres, B. A., Kominsky, S., Perrin, G. Q., Hobeika, A. C., Johnson, H. M. (2001). Superantigens: The Good, the Bad, and the Ugly. Exp. Biol. Med. 226: 164-176 [Abstract] [Full Text]
Justice, J. P., Shibata, Y., Sur, S., Mustafa, J., Fan, M., Van Scott, M. R. (2001). IL-10 gene knockout attenuates allergen-induced airway hyperresponsiveness in C57BL/6 mice. Am. J. Physiol. Lung Cell. Mol. Physiol. 280: L363-L368 [Abstract] [Full Text]
Streit, J. A., Recker, T. J., Filho, F. G., Beverley, S. M., Wilson, M. E. (2001). Protective Immunity Against the Protozoan Leishmania chagasi Is Induced by Subclinical Cutaneous Infection with Virulent But Not Avirulent Organisms. J. Immunol. 166: 1921-1929 [Abstract] [Full Text]
Fayad, L., Keating, M. J., Reuben, J. M., O'Brien, S., Lee, B.-N., Lerner, S., Kurzrock, R. (2001). Interleukin-6 and interleukin-10 levels in chronic lymphocytic leukemia: correlation with phenotypic characteristics and outcome. Blood 97: 256-263 [Abstract] [Full Text]
Shin, H. D., Winkler, C., Stephens, J. C., Bream, J., Young, H., Goedert, J. J., O'Brien, T. R., Vlahov, D., Buchbinder, S., Giorgi, J., Rinaldo, C., Donfield, S., Willoughby, A., O'Brien, S. J., Smith, M. W. (2000). Genetic restriction of HIV-1 pathogenesis to AIDS by promoter alleles of IL10. Proc. Natl. Acad. Sci. USA 97: 14467-14472 [Abstract] [Full Text]
Cottrez, F., Hurst, S. D., Coffman, R. L., Groux, H. (2000). T Regulatory Cells 1 Inhibit a Th2-Specific Response In Vivo. J. Immunol. 165: 4848-4853 [Abstract] [Full Text]