Susceptibility to cyclosporin A-induced autoimmunity: Strain differences in relation to autoregulatory T cells

Cyclosporin A-induced autoimmunity (CsA-AI), also called autoimmune syngeneic graft-vs-host disease, is a thymus dependent, T cell mediated rodent animal model of disease and is considered to be an experimental model for human scleroderma. Since adoptive transfer of CsA-AI by effector T cells can be prevented by autoregulatory T cells, there may also be a role for dominant tolerance in the resistance of certain rat strains to develop clinical manifest CsA-AI LEW rats have been reported to be susceptible, whereas BN rats are resistant to CsA-AI In the present study we first demonstrate that PVG, but not DA rats, are susceptible to CsA-AI and that disease characteristics in PVG rats are comparable to LEW rats in terms of pathogenesis and T cell kinetics, although of more rapid onset and greater severity. Next, we examined whether the relative presence of autoregulatory T-helper cells, i.e. CD25(+) and/or CD45RC(low) CD4 T cells, is increased in resistant BN and DA rats. The results obtained reveal that the genetically determined CD45RC(high)/CD45RC(low) ratio, but not the percentage CD25(+) cells, within the CD4 T cell compartment of naive rats is correlated with resistance to CsA-AI in these rat strains., We conclude that the relative presence of autoregulatory T cells with a CD45RC(low) T-helper cell phenotype may be a critical determinant in susceptibility to CsA-AI. (C) 2002 Elsevier Science Ltd.