| First Author | Schüler T | Year | 1999 |
| Journal | J Exp Med | Volume | 189 |
| Issue | 5 | Pages | 803-10 |
| PubMed ID | 10049944 | Mgi Jnum | J:53801 |
| Mgi Id | MGI:1333426 | Doi | 10.1084/jem.189.5.803 |
| Citation | Schuler T, et al. (1999) T helper cell type 1-associated and cytotoxic T lymphocyte-mediated tumor immunity is impaired in interleukin 4-deficient mice. J Exp Med 189(5):803-10 |
| abstractText | 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 calls 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. |
