Induction of chronic inflammatory arthropathy and mesenchymal tumors in rats infected with HTLV-I.

Abstract

To compare the pathogenicity of HTLV-I derived from patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) and that from patients with adult T-cell leukemia (ATL), neonatal WKA rats were inoculated with either an HTLV-I-infected T-cell line (Fuk line) newly established from a HAM/TSP patient or MT-2 derived from a patient with ATL. Of 38 rats, 34 developed mesenchymal tumors (89%) only after 14 months of age, irrespective of the cell lines used. The rats inoculated with the Fuk line developed severe arthritis (27%) and anti-type II collagen antibody (64%), and less frequently, paraparesis (7%). Those inoculated with MT-2 developed paraparesis (23%), but not arthritis. Cyclophosphamide (CY) administration to induce immunosuppression in the Fuk line-inoculated rats increased the frequency of paraparesis (70%), but decreased the frequency of tumors (20%). HTLV-I proviral DNA was found in the spinal cord, sciatic nerves, tumors, and joints, whereas pX mRNA was detected in the sciatic nerves and tumors, but not in the spinal cord and joints. As a result, HTLV-I is considered to facilitate development of both chronic inflammatory arthropathy associated with autoimmunity and mesenchymal tumors in rats by experimental infection, and its pathogenicity is likely to be greatly influenced by the host immune state.