| First Author | Mizoguchi A | Year | 1996 |
| Journal | J Exp Med | Volume | 183 |
| Issue | 3 | Pages | 847-56 |
| PubMed ID | 8642289 | Mgi Jnum | J:32981 |
| Mgi Id | MGI:80469 | Doi | 10.1084/jem.183.3.847 |
| Citation | Mizoguchi A, et al. (1996) Cytokine imbalance and autoantibody production in T cell receptor-alpha mutant mice with inflammatory bowel disease. J Exp Med 183(3):847-56 |
| abstractText | Spontaneous inflammatory bowel disease (IBD) resembling human ulcerative colitis develops in mice mutant for the T cell receptor alpha gene (TCR-alpha(-/-)). TCR-alpha(-/-) mice lack TCR-alpha/beta(+) cells but contain TCR-gamma/ delta(+) cells and a small population of a unique CD4(+), TCR-(alpha(-)/beta(+(low))) cells. Since all the immunoglobulin (Ig) classes are present in these mice, help to B cells must be provided by cells other than TCR- alpha/beta(+) cells. In the present study, we found serum levels of IgG1 and IgG2 to be markedly increased in TCR- alpha(-/-) mice with IBD as compared to TCR-alpha(-/-) mice without IBD or TCR-alpha(+/-) controls. An increase in IgG1-, IgG2a- and IgA- but not IgM-secreting mesenteric lymph node (MLN) B cells was detected in TCR-alpha(-/-) mutant mice. There was also a marked increase in MLN B cells secreting autoantibody (IgG) to tropomyosin, a cytoskeletal protein. Examination of the hyperplastic MLN showed a marked increase in the number of B, TCR-delta(+), and CD4(+) TCR-alpha(-)/beta(+) cells, similar to the cell population observed at the site of colonic inflammation. Analysis of spontaneous cytokine production by MLN cells using an enzyme-linked immunospot assay, immunohistochemistry, and reverse transcription-polymerase chain reaction showed a decrease of interleukin 2 (IL-2) but a marked increase of IL-4 and interferon gamma (IFN- gamma) production in TCR-alpha(-/-) mice with IBD as compared to TCR-alpha(-/-) mice without IBD and TCR alpha(+/-) control mice. Both TCR-alpha(-)/beta(+) and TCR- delta(+) cells were found to be capable of producing IL-4; IFN-gamma was produced mostly by non-T cells, many of which were shown to be CD3(-) NK 1.1(+) cells. We propose that the cytokine imbalance present in these mice results in expansion of B cells, production and switching of autoantibodies to IgG2 subclass, and development of IBD. It is possible that the unusual CD4(+) TCR-alpha(-)/ beta(+) population and expanded TCR-gamma(-)/delta(+) population present in TCR-alpha(-/-) mice plays a central role in this abnormal immune response. |
