| First Author | Peng SL | Year | 1998 |
| Journal | Clin Exp Immunol | Volume | 111 |
| Issue | 1 | Pages | 107-16 |
| PubMed ID | 9472669 | Mgi Jnum | J:45448 |
| Mgi Id | MGI:1195438 | Doi | 10.1046/j.1365-2249.1998.00424.x |
| Citation | Peng SL, et al. (1998) Pathogenesis of autoimmunity in alphabeta T cell-deficient lupus-prone mice. Clin Exp Immunol 111(1):107-16 |
| abstractText | Murine lupus in MRL mice has been strongly attributed to alphabeta T cell-dependent mechanisms. Non-alphabeta T cell-dependent mechanisms, such as gammadelta T cells, have been shown to drive antibody and autoantibody production, but they have not been considered capable of inducing end-organ disease. Here, we have expanded upon the findings of such previous work by examining the mechanism and extent of end-organ disease attainable via gammadelta T cells and/or non-alphabeta T cell-dependent mechanisms, assessing two prototypical lupus lesions, renal and skin disease, in TCR alpha -/- MRL mice that possessed either functional or defective Fas antigen (Fas + or lpr). Observed to 1 year of age, TCR alpha -/- MRL mice developed disease characterized by increased mortality, overt renal disease and skin lesions. While delayed in onset and/or reduced in severity compared with TCR alpha +/+ MRL/lpr animals, renal and skin lesions in alphabeta T cell-deficient animals were clearly increased in severity compared with age-matched control non-autoimmune mice. In contrast to TCR alpha +/+ MRL mice, whose disease reflected pan-isotype immune complex deposition with significant complement fixation, renal disease in TCR alpha -/- MRL animals reflected predominantly IgG1 immune complex deposition, with poor complement fixation. Thus, this study demonstrates conclusively that non-alphabeta T cell-dependent mechanisms can induce renal and skin injury in murine lupus, but at least in the kidney, only via humoral autoimmunity of a relatively non-pathological isotype which results in the delayed onset of end-organ damage. |
