Abstract
We have shown previously that normal mice given interferon-alpha/beta (IFN-alpha/beta) or tumour necrosis factor-alpha (TNF-alpha) develop marked intestinal pathology which is similar to that found in enteropathies associated with cell-mediated immunity in vivo, such as graft-versus-host reaction (GVHR). The enteropathy induced by IFN-alpha/beta and GVHR are both dependent on the presence of natural killer (NK) cells and here we have examined whether NK cells are also required for enteropathy caused by TNF-alpha. Mice injected with recombinant TNF-alpha displayed enhanced splenic NK cell activity and developed significant villus atrophy and crypt hypertrophy in the small intestine. Administration of anti-asialo GM1 antibody abolished the NK cell activity in both normal and TNF-alpha-injected mice, but had no effect on the enteropathy caused by TNF-alpha. We conclude that NK cells are not required for TNF-alpha to damage the small intestine.
Full text
PDF


Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Borland A., Mowat A. M., Parrott D. M. Augmentation of intestinal and peripheral natural killer cell activity during the graft-versus-host reaction in mice. Transplantation. 1983 Nov;36(5):513–519. doi: 10.1097/00007890-198311000-00009. [DOI] [PubMed] [Google Scholar]
- Cleveland M. G., Annable C. R., Klimpel G. R. In vivo and in vitro production of IFN-beta and IFN-gamma during graft vs host disease. J Immunol. 1988 Nov 15;141(10):3349–3356. [PubMed] [Google Scholar]
- Cleveland M. G., Lane R. G., Klimpel G. R. Enhanced interferon-alpha/beta (IFN-alpha/beta) and defective IFN-gamma production in chronic graft versus host disease: a potential mechanism for immunosuppression. Cell Immunol. 1987 Nov;110(1):120–130. doi: 10.1016/0008-8749(87)90106-7. [DOI] [PubMed] [Google Scholar]
- Degliantoni G., Murphy M., Kobayashi M., Francis M. K., Perussia B., Trinchieri G. Natural killer (NK) cell-derived hematopoietic colony-inhibiting activity and NK cytotoxic factor. Relationship with tumor necrosis factor and synergism with immune interferon. J Exp Med. 1985 Nov 1;162(5):1512–1530. doi: 10.1084/jem.162.5.1512. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garside P., Felstein M. V., Green E. A., Mowat A. M. The role of interferon alpha/beta in the induction of intestinal pathology in mice. Immunology. 1991 Oct;74(2):279–283. [PMC free article] [PubMed] [Google Scholar]
- Garside P., Hutton A. K., Severn A., Liew F. Y., Mowat A. M. Nitric oxide mediates intestinal pathology in graft-vs.-host disease. Eur J Immunol. 1992 Aug;22(8):2141–2145. doi: 10.1002/eji.1830220827. [DOI] [PubMed] [Google Scholar]
- Gordon C., Wofsy D. Effects of recombinant murine tumor necrosis factor-alpha on immune function. J Immunol. 1990 Mar 1;144(5):1753–1758. [PubMed] [Google Scholar]
- Kvale D., Brandtzaeg P., Løvhaug D. Up-regulation of the expression of secretory component and HLA molecules in a human colonic cell line by tumour necrosis factor-alpha and gamma interferon. Scand J Immunol. 1988 Sep;28(3):351–357. doi: 10.1111/j.1365-3083.1988.tb01460.x. [DOI] [PubMed] [Google Scholar]
- MacDonald T. T., Ferguson A. Hypersensitivity reactions in the small intestine. III. The effects of allograft rejection and of graft-versus-host disease on epithelial cell kinetics. Cell Tissue Kinet. 1977 Jul;10(4):301–312. [PubMed] [Google Scholar]
- MacDonald T. T., Hutchings P., Choy M. Y., Murch S., Cooke A. Tumour necrosis factor-alpha and interferon-gamma production measured at the single cell level in normal and inflamed human intestine. Clin Exp Immunol. 1990 Aug;81(2):301–305. doi: 10.1111/j.1365-2249.1990.tb03334.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mahida Y. R., Wu K., Jewell D. P. Enhanced production of interleukin 1-beta by mononuclear cells isolated from mucosa with active ulcerative colitis of Crohn's disease. Gut. 1989 Jun;30(6):835–838. doi: 10.1136/gut.30.6.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mowat A. M. Antibodies to IFN-gamma prevent immunologically mediated intestinal damage in murine graft-versus-host reaction. Immunology. 1989 Sep;68(1):18–23. [PMC free article] [PubMed] [Google Scholar]
- Mowat A. M., Felstein M. V. Experimental studies of immunologically mediated enteropathy. II. Role of natural killer cells in the intestinal phase of murine graft-versus-host reaction. Immunology. 1987 Jun;61(2):179–183. [PMC free article] [PubMed] [Google Scholar]
- Mowat A. M., Ferguson A. Intraepithelial lymphocyte count and crypt hyperplasia measure the mucosal component of the graft-versus-host reaction in mouse small intestine. Gastroenterology. 1982 Aug;83(2):417–423. [PubMed] [Google Scholar]
- Nestel F. P., Price K. S., Seemayer T. A., Lapp W. S. Macrophage priming and lipopolysaccharide-triggered release of tumor necrosis factor alpha during graft-versus-host disease. J Exp Med. 1992 Feb 1;175(2):405–413. doi: 10.1084/jem.175.2.405. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ostensen M. E., Thiele D. L., Lipsky P. E. Tumor necrosis factor-alpha enhances cytolytic activity of human natural killer cells. J Immunol. 1987 Jun 15;138(12):4185–4191. [PubMed] [Google Scholar]
- Piguet P. F., Grau G. E., Allet B., Vassalli P. Tumor necrosis factor/cachectin is an effector of skin and gut lesions of the acute phase of graft-vs.-host disease. J Exp Med. 1987 Nov 1;166(5):1280–1289. doi: 10.1084/jem.166.5.1280. [DOI] [PMC free article] [PubMed] [Google Scholar]
