ALTERED IMMUNE-RESPONSES IN INTERLEUKIN-10 TRANSGENIC MICE

Interleukin (IL)-10 is a pleiotropic cytokine which inhibits a broad a rray of immune parameters including T helper cell type 1 (Th1) cytokin e production, antigen presentation, and antigen-specific T cell, proli feration. To understand the consequences of altered expression of IL-1 0 in immune models of autoimmune disease, the response to infectious a gents, and the response to tumors, we developed transgenic mice expres sing IL-10 under the control of the IL-2 promoter. Upon in vitro stimu lation, spleen cells from unimmunized transgenic mice secrete higher l evels of IL-10 and lower amounts of IFN-gamma than do controls, althou gh no gross abnormalities were detected in lymphocyte populations or s erum Ig levels. Transfer of normally pathogenic CD4(+) CD45RB(high) sp lenic T cells from IL-10 transgenic mice did not cause colitis in reci pient severe combined immunodeficiency mice. Furthermore, co-transfer of these transgenic cells with CD4(+) CD45RB(high) T cells from contro l mice prevented disease. Transgenic mice retained their resistance to Leishmania major infection, indicating that their cell-mediated immun e responses were not globally suppressed. Lastly, in comparison to con trols, IL-10 transgenic mice were unable to limit the growth of immuno genic tumors. Administration of blocking IL-10 mAbs restored in vivo a ntitumor responses in the transgenic mice. These results demonstrate t hat a single alteration in the T cell cytokine profile can lead to dra matic changes in immune responses in a manner that is stimulus depende nt. These mice will be useful in defining differences in inflammatory conditions and cellular immunity mediated by IL-10.