To elucidate the abnormality of T cell differentiation in nude mice grafted with rat fetal thymus that develop multiple-organ-localized autoimmune diseases, we examined sequential appearance of T cell subsets and expression of TCR genes in BALB/c nude mice after grafting with fetal F344 rat thymus. We observed progressive expression of TCRγ/δ-α/β genes in the lymph node (LN) cells from 8 to 12 wk after grafting. An appreciable number of CD4+ T cells but few CD8+ T cells were detected in the LN at 8 wk after grafting. CD8+ T cells increased slowly in number by 12 wk after grafting but remained at a low level in comparison with those in nude mice 12 wk after grafting with BALB/c thymus. In correlation with an increase in the number of T cells expressing TCR α/β genes, alloreactivity as assessed by MLR was increased to a normal level. However, CTL activity against alloantigens remained at a low level in the LN cells at 12 wk. At this stage, organ-specific autoimmune diseases and a high level of anti-DNA autoantibodies were detected. In these mice host-reactive T cells such as Vβ3- or Vβ11-bearing T cells were virtually eliminated in the peripheral mature T cell pool, whereas T cells maturing in the fetal rat thymus significantly proliferated in response to donor-rat stimulator cells. These results suggest that the development of the autoimmune diseases may be ascribed to an impaired maturation of CD8+ T cells but not to failure in clonal elimination of host-reactive T cells in nude mice grafted with rat thymus.
|Number of pages||8|
|Journal||Journal of Immunology|
|Publication status||Published - 1990|
All Science Journal Classification (ASJC) codes
- Immunology and Allergy