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| Item Type: | Article |
|---|---|
| Title: | T helper cell type 1-associated and cytotoxic T lymphocyte-mediated tumor immunity is impaired in interleukin 4-deficient mice |
| Creators Name: | Schueler, T. and Qin, Z. and Ibe, S. and Noben-Trauth, N. and Blankenstein, T. |
| Abstract: | It is widely accepted that cellular immune responses are induced by CD4(+) T helper 1 (Th1) cells secreting interleukin (IL)-2 and interferon (IFN)-gamma. Tumor immunity is often mediated by cytotoxic T lymphocytes (CTLs) whose activation is supported by Th1 cytokines. Since IL-4 directs Th2 development and has been shown to inhibit Th1-dominated responses, we assumed that IL-4-deficient (IL-4(-/-)) mice would develop vigorous CTL-mediated tumor immunity compared with IL-4-competent (IL-4(+/+)) mice. Surprisingly, IL-4(-/-) mice were severely impaired to develop tumor immunity to both a mammary adenocarcinoma line and a colon carcinoma line. The lack of tumor immunity in IL-4(-/-) mice was associated with reduced IFN-gamma production, diminished levels of tumor-reactive serum IgG2a, and undetectable CTL activity, indicating a defective Th1 response in the absence of endogenous IL-4. Anti-IL-4 monoclonal antibody blocked tumor immunity in IL-4(+/+) mice when administered at the time of immunization but not at the time of challenge. Additionally, tumor immunity could be induced in IL-4(-/-) mice, if IL-4 was provided by gene-modified cells together with immunizing tumor cells. These results demonstrate that tumor immunity requires IL-4 in the priming phase for the generation of effector cells rather than for their maintenance and exclude secondary, developmental defects in the "knockout" strain. Together, our results demonstrate a novel and previously unanticipated role of IL-4 for the generation of Th1-associated, CTL-mediated tumor immunity. |
| Keywords: | Tumor Vaccination, Interleukin 4, T Cell Immunity, Interleukin 4-Deficient Mice, Animals, Mice |
| Source: | Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Volume: | 189 |
| Number: | 5 |
| Page Range: | 803-810 |
| Date: | 1 March 1999 |
| Official Publication: | http://www.jem.org/cgi/content/abstract/189/5/803 |
| PubMed: | View item in PubMed |
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