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 neurologic disease, HTLV-I-associated myelopathy-tropical spastic paraparesis, in which both pathological and immunological changes are observed within the central nervous system. The pathogenesis of infection in HTLV-I-associated myopathy-tropical spastic paraparesis is not well understood with respect to the cell tropism of HTLV-I and its relationship to the destruction of neural elements. In this study, neuroblastoma cells were infected with HTLV-I by coculturing with HUT-102 cells to demonstrate that cells of neuronal origin are susceptible to this retroviral infection. HTLV-I infection of the neuroblastoma cells was confirmed by verifying the presence of HTLV-I gp46 surface antigens by flow cytometry and by verifying the presence of HTLV-I pX RNA by Northern (RNA) blotting and in situ hybridization techniques. To determine whether HTLV-I infection could potentially lead to changes in cell surface recognition 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 expression and RNA transcripts, to express HLA classes I and II. In contrast, cocultured neuroblastoma cells that did not become infected with HTLV-I expressed only HLA class I. HLA class I expression was enhanced by the cytokines tumor necrosis factor alpha and gamma interferon and in the presence of HUT-102 supernatant. In this system, expression of HLA class I and II molecules appeared to be regulated by different mechanisms. HLA class I expression was probably induced by cytokines present in the HUT-102 supernatant and was not dependent on HTLV-I infection. HLA class II expression required HTLV-I infection of the cells. The observation of HTLV-I infection leading to HLA induction in these neuroblastoma cells provides a possible mechanism for immunologic recognition of infected neuronal cells.
Lehky
T J
TJ
Neuroimmunology Branch, NINDS, NIH, Bethesda, MD 20892.
Cowan
E P
EP
Lampson
L A
LA
Jacobson
S
S
D002450:Cell Communication; D016207:Cytokines / Q000494:pharmacology; D015485:Deltaretrovirus Antigens / Q000096:biosynthesis / Q000302:isolation & purification; D005786:Gene Expression Regulation / Q000187:drug effects; D015686:Gene Products, env / Q000096:biosynthesis; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D017403:In Situ Hybridization; D009447:Neuroblastoma / Q000276:immunology / Q000382:microbiology; D009474:Neurons / Q000276:immunology* / Q000382:microbiology*; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000302:isolation & purification; D015682:Retroviridae Proteins, Oncogenic / Q000096:biosynthesis; D013564:Sympathetic Nervous System / Q000276:immunology / Q000382:microbiology; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000382:microbiology
D016207:Cytokines; D015485:Deltaretrovirus Antigens; D015686:Gene Products, env; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D012367:RNA, Viral; D015682:Retroviridae Proteins, Oncogenic; C055266:gp46 protein, Human T-cell leukemia virus type I