Altered immune responses in interleukin 10 transgenic mice.
Interleukin (IL)-10 is a pleiotropic cytokine which inhibits a broad array of immune parameters including T helper cell type 1 (Th1) cytokine production, antigen presentation, and antigen-specific T cell proliferation. To understand the consequences of altered expression of IL-10 in immune models of autoimmune disease, the response to infectious agents, and the response to tumors, we developed transgenic mice expressing IL-10 under the control of the IL-2 promoter. Upon in vitro stimulation, spleen cells from unimmunized transgenic mice secrete higher levels of IL-10 and lower amounts of IFN-gamma than do controls, although no gross abnormalities were detected in lymphocyte populations or serum Ig levels. Transfer of normally pathogenic CD4(+) CD45RBhigh splenic T cells from IL-10 transgenic mice did not cause colitis in recipient severe combined immunodeficiency mice. Furthermore, co-transfer of these transgenic cells with CD4(+) CD45RBhigh T cells from control mice prevented disease. Transgenic mice retained their resistance to Leishmania major infection, indicating that their cell-mediated immune responses were not globally suppressed. Lastly, in comparison to controls, IL-10 transgenic mice were unable to limit the growth of immunogenic tumors. Administration of blocking IL-10 mAbs restored in vivo antitumor responses in the transgenic mice. These results demonstrate that a single alteration in the T cell cytokine profile can lead to dramatic changes in immune responses in a manner that is stimulus dependent. These mice will be useful in defining differences in inflammatory conditions and cellular immunity mediated by IL-10.
Hagenbaugh
A
A
Molecular Biology Institute, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA.
Sharma
S
S
Dubinett
S M
SM
Wei
S H
SH
Aranda
R
R
Cheroutre
H
H
Fowell
D J
DJ
Binder
S
S
Tsao
B
B
Locksley
R M
RM
Moore
K W
KW
Kronenberg
M
M
D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000517:prevention & control; D005260:Female; D007109:Immunity; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D016753:Interleukin-10