ts1, a temperature-sensitive mutant of Moloney murine leukemia virus TB, can infect both CD4+ and CD8+ T cells but requires CD4+ T cells in order to cause paralysis and immunodeficiency.
When neonatal FVB/N mice were inoculated with ts1, a temperature-sensitive mutant of Moloney murine leukemia virus TB, they developed a progressive bilateral hindlimb paralysis and immunodeficiency leading to death 4 to 6 weeks after inoculation. T lymphocytes have been shown to be primarily responsible for this ts1-induced syndrome. Here we compare the role played by each subset of T lymphocytes, i.e., CD4+ and CD8+ T cells, in disease development. Mice were depleted of a specific subset for the first 10 days of their lives by using either anti-CD4 or anti-CD8 monoclonal antibodies in vivo. Disease development in these mice was then monitored. Depletion of CD4+ T cells significantly attenuated the ts1-induced syndrome: virus replication was decreased, disease latency was extended, and death was prevented in 60% of the mice. Similar treatment with anti-CD8 antibody had almost no effect on disease progression. However, when depletion was begun 2 weeks after neonatal ts1 inoculation, CD4+ T cell depletion did not affect disease development. ts1 infected CD4+ and CD8+ T lymphocytes equally well in vivo, as shown by flow cytometric analysis, but virus replication was restricted primarily to the CD4+ subset of T cells, as found by in vitro assay. Hence, CD4+ T lymphocytes play an important role in the development of ts1-induced paralysis and immunodeficiency. The mechanism of this CD4+ T-cell-mediated disease production by ts1 is not clear; however, increased replication of ts1 in the CD4+ T cells, especially in the early stages of the disease, seems to play a crucial role.
University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville 78957.
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Wong
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D016827:CD8 Antigens / Q000276:immunology; D006614:Hindlimb / Q000473:pathology; D006942:Hypergammaglobulinemia / Q000209:etiology; D007121:Immunocompetence; D007942:Leukemia, Experimental / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000472:pathogenicity*; D009154:Mutation; D010243:Paralysis / Q000209:etiology; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000382:microbiology*; D013950:Thymus Gland / Q000382:microbiology; D014779:Virus Replication
D015704:CD4 Antigens; D016827:CD8 Antigens