INDUCTION OF HLA CLASS-I AND CLASS-II EXPRESSION IN HUMAN T-LYMPHOTROPIC VIRUS TYPE I-INFECTED NEUROBLASTOMA-CELLS

Human T-lymphotropic virus type I (HTLV-I) is associated with a neurol ogic disease, HTLV-I-associated myelopathy-tropical spastic paraparesi s, in which both pathological and immunological changes are observed w ithin the central nervous system. The pathogenesis of infection in HTL V-I-associated myopathy-tropical spastic paraparesis is not well under stood with respect to the cell tropism of HTLV-I and its relationship to the destruction of neural elements. In this study, neuroblastoma ce lls were infected with HTLV-I by coculturing with HUT-102 cells to dem onstrate that cells of neuronal origin are susceptible to this retrovi ral infection. HTLV-I infection of the neuroblastoma cells was confirm ed by verifying the presence of HTLV-I gp46 surface antigens by flow c ytometry and by verifying the presence of HTLV-I pX RNA by Northern (R NA) blotting and in situ hybridization techniques. To determine whethe r HTLV-I infection could potentially lead to changes in cell surface r ecognition by the immune system, the infected neuroblastoma cells were analyzed for altered HLA expression. The HTLV-I-infected, cocultured neuroblastoma cells were shown, through cell surface antigen expressio n and RNA transcripts, to express HLA classes I and II. In contrast, c ocultured neuroblastoma cells that did not become infected with HTLV-I expressed only HLA class I. HLA class I expression was enhanced by th e cytokines tumor necrosis factor alpha and gamma interferon and in th e presence of HUT-102 supernatant. In this system, expression of HLA c lass I and II molecules appeared to be regulated by different mechanis ms. HLA class I expression was probably induced by cytokines present i n the HUT-102 supernatant and was not dependent on HTLV-I infection. H LA class II expression required HTLV-I infection of the cells. The obs ervation of HTLV-I infection leading to HLA induction in these neurobl astoma cells provides a possible mechanism for immunologic recognition of infected neuronal cells.