Journal of Experimental Medicine, Vol 176, 1091-1098, Copyright © 1992 by Rockefeller University Press

ARTICLES

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

RA Seder, WE Paul, MM Davis and B Fazekas de St. Groth
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.

To study the factors that determine whether CD4+ T cells produce interleukin 4 (IL-4) or interferon gamma (IFN-gamma) upon stimulation we used a system allowing naive T cells to be primed in vitro by specific antigen. Dense CD4+ T cells were purified from mice that expressed transgenes encoding a T cell receptor specific for pigeon cytochrome C peptide 88-104 in association with I-Ek. These T cells produced very limited amounts of IL-4 and IFN-gamma upon immediate challenge with 88-104 and antigen-presenting cells (APC). However, after an initial "priming" culture in which they were incubated for 4 d in the presence of 88-104, APC, and 1,000 U/ml IL-4, the T cells acquired the capacity to produce substantial amounts of IL-4 upon rechallenge but made very little IFN-gamma. Cells primed in the absence of IL-4 produced IFN-gamma upon rechallenge but virtually no IL-4. The inhibitory effect of IL-4 on IFN-gamma production did not appear to be mediated by the induction of IL-10 production since IL-10 addition to initial cultures did not suppress priming for IFN-gamma production, nor did anti-IL-10 block the inhibitory effect of IL-4. IFN-gamma itself did not increase priming for IFN-gamma production, nor did anti-IFN- gamma reduce such priming. IFN-gamma did, however, diminish priming for IL-4 production when limiting amounts of IL-4 (100 U/ml) were used in the initial culture. The dominant effect of IL-4 in determining the lymphokine-producing phenotype of primed cells was observed with dendritic cells (DC), activated B cells, and I-Ek-transfected fibroblasts as APC. However, the different APC did vary in their potency, with DC being superior to activated B cells, which were superior to transfected fibroblasts.
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• Cianferoni, A., Schroeder, J. T., Kim, J., Schmidt, J. W., Lichtenstein, L. M., Georas, S. N., Casolaro, V. (2001). Selective inhibition of interleukin-4 gene expression in human T cells by aspirin. Blood 97: 1742-1749 [Abstract] [Full Text]  
• Maier, L.A., Sawyer, R.T., Tinkle, S.S., Kittle, L.A., Barker, E.A., Balkissoon, R., Rose, C., Newman, L.S. (2001). IL-4 fails to regulate in vitro beryllium-induced cytokines in berylliosis. Eur Respir J 17: 403-415 [Abstract] [Full Text]  
• Delgado, M., Ganea, D. (2001). Cutting Edge: Is Vasoactive Intestinal Peptide a Type 2 Cytokine?. J. Immunol. 166: 2907-2912 [Abstract] [Full Text]  
• Ben-Sasson, S. Z., Gerstel, R., Hu-Li, J., Paul, W. E. (2001). Cell Division Is Not a ""Clock"" Measuring Acquisition of Competence to Produce IFN-{{gamma}} or IL-4. J. Immunol. 166: 112-120 [Abstract] [Full Text]  
• Yang, W.-C., Ching, K. A., Tsoukas, C. D., Berg, L. J. (2001). Tec Kinase Signaling in T Cells Is Regulated by Phosphatidylinositol 3-Kinase and the Tec Pleckstrin Homology Domain. J. Immunol. 166: 387-395 [Abstract] [Full Text]  
• Ebner, S., Ratzinger, G., Krosbacher, B., Schmuth, M., Weiss, A., Reider, D., Kroczek, R. A., Herold, M., Heufler, C., Fritsch, P., Romani, N. (2001). Production of IL-12 by Human Monocyte-Derived Dendritic Cells Is Optimal When the Stimulus Is Given at the Onset of Maturation, and Is Further Enhanced by IL-4. J. Immunol. 166: 633-641 [Abstract] [Full Text]  
• Kacha, A. K., Fallarino, F., Markiewicz, M. A., Gajewski, T. F. (2000). Spontaneous Rejection of Poorly Immunogenic P1.HTR Tumors by Stat6-Deficient Mice. J. Immunol. 165: 6024-6028 [Abstract] [Full Text]  
• Brunner, C., Seiderer, J., Schlamp, A., Bidlingmaier, M., Eigler, A., Haimerl, W., Lehr, H.-A., Krieg, A. M., Hartmann, G., Endres, S. (2000). Enhanced Dendritic Cell Maturation by TNF-{alpha} or Cytidine-Phosphate-Guanosine DNA Drives T Cell Activation In Vitro and Therapeutic Anti-Tumor Immune Responses In Vivo. J. Immunol. 165: 6278-6286 [Abstract] [Full Text]  
• Wagner, E. F., Hanna, N., Fast, L. D., Kouttab, N., Shank, P. R., Vazquez, A., Sharma, S. (2000). Novel Diversity in IL-4-Mediated Responses in Resting Human Naive B Cells Versus Germinal Center/Memory B Cells. J. Immunol. 165: 5573-5579 [Abstract] [Full Text]  
• Noben-Trauth, N., Hu-Li, J., Paul, W. E. (2000). Conventional, Naive CD4+ T Cells Provide an Initial Source of IL-4 During Th2 Differentiation. J. Immunol. 165: 3620-3625 [Abstract] [Full Text]  

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