IL-4 Exacerbates Disease in a Th1 Cell Transfer Model of Colitis

IL-4 is associated with Th2-type immune responses and can either inhibit or, in some cases, promote Th1-type responses. We tested the effect of IL-4 treatment on the development of inflammation in the CD4(+)CD45RB(high) T cell transfer model of colitis, which has been characterized as a Th1-dependen...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2001-02, Vol.166 (4), p.2793-2800
Main Authors: Fort, Madeline M, Lesley, Robin, Davidson, Natalie J, Menon, Satish, Brombacher, Frank, Leach, Michael W, Rennick, Donna M
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - administration & dosage
Adoptive Transfer - methods
Animals
CD4 Antigens - biosynthesis
Cell Movement - genetics
Cell Movement - immunology
Colitis - classification
Colitis - genetics
Colitis - immunology
Colitis - pathology
Colitis, Ulcerative - genetics
Colitis, Ulcerative - immunology
Colitis, Ulcerative - pathology
Colon - immunology
Colon - pathology
Disease Models, Animal
Epithelial Cells - immunology
Epithelial Cells - pathology
Hyperplasia
Injections, Intraperitoneal
Interleukin-4 - administration & dosage
Interleukin-4 - deficiency
Interleukin-4 - genetics
Leukocyte Common Antigens - biosynthesis
Mice
Mice, Inbred BALB C
Mice, Knockout
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
T-Lymphocyte Subsets - transplantation
Th1 Cells - immunology
Th1 Cells - metabolism
Th1 Cells - transplantation
Th2 Cells - immunology
Th2 Cells - metabolism
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Summary:IL-4 is associated with Th2-type immune responses and can either inhibit or, in some cases, promote Th1-type responses. We tested the effect of IL-4 treatment on the development of inflammation in the CD4(+)CD45RB(high) T cell transfer model of colitis, which has been characterized as a Th1-dependent disease. IL-4 treatment significantly accelerated the development of colitis in immunodeficient recipients (recombinase-activating gene-2 (Rag2)(-/-)) of CD4(+)CD45RB(high) T cells. Quantitative analysis of mRNA expression in the colons of IL-4-treated mice showed an up-regulation of both Th1- and Th2-associated molecules, including IFN-gamma, IP-10, MIG, CXCR3, chemokine receptor-8, and IL-4. However, cotreatment with either IL-10 or anti-IL-12 mAb effectively blocked the development of colitis in the presence of exogenous IL-4. These data indicate that IL-4 treatment exacerbates a Th1-mediated disease rather than induces Th2-mediated inflammation. As other cell types besides T cells express the receptor for IL-4, the proinflammatory effects of IL-4 on host cells in Rag2(-/-) recipients were assessed. IL-4 treatment was able to moderately exacerbate colitis in Rag2(-/-) mice that were reconstituted with IL-4Ralpha-deficient (IL-4Ralpha(-/-)) CD4(+)CD45RB(high) T cells, suggesting that the IL-4 has proinflammatory effects on both non-T and T cells in this model. IL-4 did not cause colitis in Rag2(-/-) mice in the absence of T cells, but did induce an increase in MHC class II expression in the lamina propria of the colon, which was blocked by cotreatment with IL-10. Together these results indicate that IL-4 can indirectly promote Th1-type inflammation in the CD4(+)CD45RB(high) T cell transfer model of colitis.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.166.4.2793