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...

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Veröffentlicht in:The Journal of experimental medicine Jg. 185; H. 12; S. 2101
Hauptverfasser: Hagenbaugh, A, Sharma, S, Dubinett, S M, Wei, S H, Aranda, R, Cheroutre, H, Fowell, D J, Binder, S, Tsao, B, Locksley, R M, Moore, K W, Kronenberg, M
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 16.06.1997
Schlagworte:
Animals
Cells, Cultured
Colitis - prevention & control
Female
Immunity
Interleukin-10 - genetics
Interleukin-10 - physiology
Leishmaniasis, Cutaneous - immunology
Lung Neoplasms - immunology
Lymphocytes - physiology
Male
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Transgenic
ISSN:0022-1007
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:0022-1007
DOI:10.1084/jem.185.12.2101