Interleukin 10 pretreatment protects target cells from tumor- and allo- specific cytotoxic T cells and downregulates HLA class I expression

doi:10.1084/jem.180.6.2371

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Interleukin 10 pretreatment protects target cells from tumor- and allo- specific cytotoxic T cells and downregulates HLA class I expression

M Matsuda, F Salazar, M Petersson, G Masucci, J Hansson, P Pisa, QJ Zhang, MG Masucci and R Kiessling
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.

Interleukin 10 (IL-10) is a cytokine with a variety of reported effects including inhibition of monocyte major histocompatibility complex (MHC) class II-dependent antigen presentation, type 1 helper T cell cytokine production, and inhibition of T cell proliferation. Herein we report the effect of IL-10 pretreatment on antigen presentation to tumor- and allo-specific CD8+ cytotoxic T lymphocytes (CTL). Prior incubation of human melanoma cells with recombinant IL-10 (rIL-10) for 48-72 h resulted in a dose-dependent, up to 100% inhibition, of autologous CTL- mediated, HLA-A2.1-restricted, tumor-specific lysis. Allo-specific CTL cytotoxicity against Epstein-Barr virus-transformed lymphoblastoid cell lines (LCL) was also inhibited, demonstrating a protective effect also on lymphoid cells. In contrast, IL-10 pretreatment of allogeneic LCL or K562 targets had either no effect or slightly enhanced cytotoxic activity mediated by freshly isolated or IL-2-activated natural killer cells. Flow cytometric analysis with monoclonal antibodies against HLA- A2, or nonpolymorphic determinants of MHC class I proteins, revealed a 20-50% reduction in cell-surface expression, whereas intercellular adhesion molecules 1, and 2, and lymphocyte function-associated antigen 3 levels were not affected. In addition, relative to untreated target cells, IL-10 pretreated tumor cells were unaltered in their capacity to affect CTL-mediated lysis by cold target inhibition, demonstrating that the effect of IL-10 is unrelated to the initial binding of CTL to their targets. These results are compatible with an effect of IL-10 on the MHC class I antigen presentation pathway, and suggest a novel mechanism of immune tolerance, based on escape from CTL-mediated tumor and allo- transplant rejection.
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Asadullah, K., Sterry, W., Volk, H. D. (2003). Interleukin-10 Therapy--Review of a New Approach. Pharmacol. Rev. 55: 241-269 [Abstract] [Full Text]
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Moreau, P., Adrian-Cabestre, F., Menier, C., Guiard, V., Gourand, L., Dausset, J., Carosella, E. D., Paul, P. (1999). IL-10 selectively induces HLA-G expression in human trophoblasts and monocytes. Int Immunol 11: 803-811 [Abstract] [Full Text]
Chakraborty, N. G., Li, L., Sporn, J. R., Kurtzman, S. H., Ergin, M. T., Mukherji, B. (1999). Emergence of Regulatory CD4+ T Cell Response to Repetitive Stimulation with Antigen-Presenting Cells In Vitro: Implications in Designing Antigen-Presenting Cell-Based Tumor Vaccines. J. Immunol. 162: 5576-5583 [Abstract] [Full Text]
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Boulland, M.-L., Meignin, V., Leroy-Viard, K., Copie-Bergman, C., Briere, J., Touitou, R., Kanavaros, P., Gaulard, P. (1998). Human Interleukin-10 Expression in T/Natural Killer-Cell Lymphomas : Association with Anaplastic Large Cell Lymphomas and Nasal Natural Killer-Cell Lymphomas. Am. J. Pathol. 153: 1229-1237 [Abstract] [Full Text]
Petersson, M., Charo, J., Salazar-Onfray, F., Noffz, G., Mohaupt, M., Qin, Z., Klein, G., Blankenstein, T., Kiessling, R. (1998). Constitutive IL-10 Production Accounts for the High NK Sensitivity, Low MHC Class I Expression, and Poor Transporter Associated with Antigen Processing (TAP)-1/2 Function in the Prototype NK Target YAC-1. J. Immunol. 161: 2099-2105 [Abstract] [Full Text]
Eskdale, J., Gallagher, G., Verweij, C. L., Keijsers, V., Westendorp, R. G.�J., Huizinga, T. W.�J. (1998). Interleukin 10�secretion in relation to human IL-10 locus haplotypes. Proc. Natl. Acad. Sci. USA 95: 9465-9470 [Abstract] [Full Text]
Lee, S. P., Constandinou, C. M., Thomas, W. A., Croom-Carter, D., Blake, N. W., Murray, P. G., Crocker, J., Rickinson, A. B. (1998). Antigen Presenting Phenotype of Hodgkin Reed-Sternberg Cells: Analysis of the HLA Class I Processing Pathway and the Effects of Interleukin-10 on Epstein-Barr Virus-Specific Cytotoxic T-Cell Recognition. Blood 92: 1020-1030 [Abstract] [Full Text]
Zeidler, R., Eissner, G., Meissner, P., Uebel, S., Tampe, R., Lazis, S., Hammerschmidt, W. (1997). Downregulation of TAP1 in B Lymphocytes by Cellular and Epstein-Barr Virus-Encoded Interleukin-10. Blood 90: 2390-2397 [Abstract] [Full Text]
Hagenbaugh, A., Sharma, S., Dubinett, S. M., Wei, S. H.-Y., Aranda, R., Cheroutre, H., Fowell, D. J., Binder, S., Tsao, B., Locksley, R. M., Moore, K. W., Kronenberg, M. (1997). Altered Immune Responses in Interleukin 10�Transgenic Mice. JEM 185: 2101-2110 [Abstract] [Full Text]
Oudejans, J.J., Jiwa, N.M., Kummer, J.A., Ossenkoppele, G.J., van Heerde, P., Baars, J.W., Kluin, Ph.M., Kluin-Nelemans, J.C., van Diest, P.J., Middeldorp, J.M., Meijer, C.J.L.M. (1997). Activated Cytotoxic T Cells as Prognostic Marker in Hodgkin's Disease. Blood 89: 1376-1382 [Abstract] [Full Text]