| First Author | Koh WP | Year | 1999 |
| Journal | J Immunol | Volume | 162 |
| Issue | 12 | Pages | 7208-16 |
| PubMed ID | 10358167 | Mgi Jnum | J:111186 |
| Mgi Id | MGI:3653169 | Doi | 10.4049/jimmunol.162.12.7208 |
| Citation | Koh WP, et al. (1999) TCR-mediated involvement of CD4+ transgenic T cells in spontaneous inflammatory bowel disease in lymphopenic mice. J Immunol 162(12):7208-16 |
| abstractText | Spontaneous colitis resembling ulcerative colitis developed in 3 of 10 independent TCR transgenic (Tg) mouse lines maintained under specific pathogen-free conditions. All three susceptible lines were CD4 lymphopenic, whereas resistant lines had normal numbers of CD4+ T cells. Thus, cytochrome c-specific 5C.C7 TCR Tg mice developed colitis only when crossed onto a SCID- or Rag-1-deficient background. A second line of lymphopenic cytochrome c-specific Tg mice bearing the AND TCR also developed colitis. In both cases, CD4+ T cells expressing the Tg-encoded TCR were preferentially activated in inflamed colons compared with lymph nodes or spleens. In contrast, Tg+CD4+ T cells remained quiescent in both inflamed and unaffected colons in another line of susceptible Tg mice carrying a TCR specific for myelin basic protein, suggesting a fortuitous cross-reactivity of the IEk-restricted cytochrome c-reactive AND and 5C.C7 TCRs with an Ag present in the gut. The percentage of CD4+ T cells expressing only endogenous TCR alpha-chains was increased consistently in inflamed colons in AND as well as 5C.C7 Rag-1-/- TCR Tg mice, suggesting that polyclonal CD4+ T cells were also involved in the pathogenesis of spontaneous colitis. Moreover, our data indicate that some alpha-chain rearrangement was still occurring in TCR Tg mice on a Rag-1-/- background, since activated CD4+ T cells expressing endogenously rearranged alpha-chains paired with the Tg-encoded beta-chain were detected consistently in the colons of such mice. |
