Age-dependent paraparesis in WKA rats: evaluation of MHC k-haplotype and HTLV-1 infection

Human T-cell leukemia virus type 1 (HTLV-I) infection is shown to be closel y associated with HTLV-l-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the occurrence of HAM/TSP was reported to be associate d with MHC class II, the mechanism is still unclear. The WKA(RT1(k)) strain of rats was reported to develop HAM/TSP-like paraparesis after HTLV-I infe ction, and was suggested to be an animal model of HAM/TSP. We asked whether MHC k-haplotype is specifically involved in the pathogenesis of paraparesi s of WKA(RT1(k)) rats. We injected the HTLV-1 producing human T cells (MT-2 cells) intravenously into WKA(RT1(k)) rats and MHC congenic WKA.1L(RT1(k)) rats which have MHC l-haplotype of LEW rats on the WKA background. Positiv e antibody response to HTLV-I antigens and presence of provirus in peripher al blood mononuclear cells confirmed that MT-2 cell-injected rats were infe cted with HTLV-1. Two of 13 MT-2 cell-injected WKA(RT1(k)) rats and five of 13 MT-2 cell-injected WKA.1L(RT1(k)) rats developed HAM/TSP-like hindlimb paraparesis between 16 and 26 months old. Interestingly, three of 14 MT-2 c ell-uninjected WKA(RT1(k)) rats and four of 13 MT-2 cell-uninjected WKA.1L( RT1(1)) rats showed similar paraparesis between 15 and 26 months old. MHC k -haplotype is not specific to the development of paraparesis in WKA(RT1(k)) rats. The role of aging, genetic background, HTLV-I infection and other fa ctors on the development of HAM/TSP-like paraparesis in rats are discussed. (C) 1999 Elsevier Science B.V. All rights reserved.