Tj. Lehky et al., INDUCTION OF HLA CLASS-I AND CLASS-II EXPRESSION IN HUMAN T-LYMPHOTROPIC VIRUS TYPE I-INFECTED NEUROBLASTOMA-CELLS, Journal of virology, 68(3), 1994, pp. 1854-1863
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.