Functional alteration of peripheral CD25 +CD4 +immunoregulatory T cells in a transgenic rat model of autoimmune diseases

Abstract

Transgenic rats carrying the env– pX gene of human T cell leukemia virus type-I (env–pX rats) develop various collagen vascular diseases. Since autoantibodies are present in their sera, env–pX rats are considered to be a prototype model for autoimmune diseases. Adoptive transfers of spleen cells from syngenic non-transgenic rats decreased the incidence of diseases in env–pX rats, thus suggesting that normal spleen contains cells, which suppress autoimmune diseases. Murine peripheral CD25 +CD4 +T cells play roles in maintaining immunological self-tolerance. To examine if alterations of immunoregulatory cells may be evident in env–pX rats, quantitative and qualitative analyses of splenic CD25 +CD4 +T cells were done before these rats developed autoimmune diseases. Env–pX and non-transgenic rats had equivalent number of CD25 +CD4 +T cells. However, CD25 +CD4 +T cells from env–pX rats did not suppress proliferation of T cells stimulated by anti-CD3 antibodies (Ab) in vitro, whereas those from non-transgenic rats did. Additionally, env–pX CD25 +CD4 +T cells showed autologous and anti-CD3 Ab-mediated proliferation, in contrast to the anergic features in non-transgenic rats. These findings appear to be the first evidence that CD25 +CD4 +immunoregulatory T cells are altered in animal models, which naturally develop autoimmune diseases.