Rudimentary thymus of SCID mouse plays an important role in the development of retrovirus-induced neurologic disorders.
The role of the thymus in neurologic disorders induced by the murine retrovirus, ts1, a neuropathogenic and lymphocytopathic mutant of the Moloney murine leukemia virus-TB, was examined using severe combined immune deficiency (SCID) mice. Athymic nude mice are resistant to ts1-induced neurologic disease. All SCID mice inoculated neonatally with ts1 developed neurologic disorders similar to those of inoculated BALB/c mice, albeit after a longer latency period. In some experiments, instead of inoculating ts1 directly, purified thymocytes, CD4+, or CD8+ T cells from ts1-infected BALB/c mice were transferred to neonatal H-2 compatible SCID mice. We found that SCID mice that received infected thymocytes developed the disease faster than those that received infected CD4+ T cells. SCID mice that received infected CD8+ T cells did not develop any disease. Thus, the (rudimentary) thymus of SCID mouse plays a key role in ts1-induced neurologic disease. In addition, flow cytometric analysis of the reconstituted SCID mice showed that CD8+ T cells migrate and preferentially colonize the thymus while CD4+ T cells were found in the spleen and to a lesser extent in the thymus. However, the significance of this organ specific movements of transferred cells in relation to the virus infection remains unclear. In view of the involvement of the thymus and the CD4+ T cells in human immunodeficiency virus infection, which also infects the central nervous system (CNS) in most cases, our findings in this murine model may help us better understand how the thymus may contribute to the damage of the CNS in retrovirus infections.
University of Texas, M.D. Anderson Cancer Center, Science Park--Research Division, Smithville 78957.
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Wong
D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D003001:Cloning, Molecular; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008979:Moloney murine leukemia virus / Q000235:genetics; D009422:Nervous System Diseases / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D012192:Retroviridae Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D013950:Thymus Gland / Q000276:immunology*; D014779:Virus Replication