1993 Fiscal Year Final Research Report Summary
Pathogenesis of HTLV-I-associated Myelopathy (HAM) ; Neuropathological Analysis and Establishment of Animal Model
| Project/Area Number |
04670494
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
神経内科学
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| Research Institution | KAHOSHIMA UNIVERSITY |
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Principal Investigator |
IZUMO Shuji FACULTY OF MED.LECTURELAR, 医学部, 講師 (30143811)
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| Co-Investigator(Kenkyū-buntansha) |
NOMOTO Masahiro FACULTY OF MED.ASSOCI.PROF., 医学部, 助教授 (50208401)
OSAME Mitsuhiro FACULTY OF MED.PROFESSOR, 医学部, 教授 (10041435)
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| Project Period (FY) |
1992 – 1993
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| Keywords | HAM / HTLV-I / Pathogenesis / Neuropatholgy / Immunohistochemistry / Autopsy / Marmoset |
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| Research Abstract |
A neuropathological analysis was performed in five autopsycases with HAM in order to clarify the pathomechanism of HAM.Histopathological findings revealed a chronic inflammatory process mainly involving the thoracic spinal cord. More than half of the infiltrated cells were positive for pan-T cell marker. The numbers of CD4 positive cells and CD8 positive cells were equally in the cases with short clinical course. CD8, however, was predominated over CD4 in the cases with longer duration of illness. Natural killer cells, IL-2R positive cells and B cells were rarely present at any stages. Some infiltrating cells, microglia and endotherial cells were positive for HLA-ABC or HLA-DR.Several cytokines such as IL-1beta, TNF-alpha, and IFN-gamma, were detected in some macrophages, astrocytes, and microglias in active inflammatory lesions. Copy numbers of HTLV-I proviral DNA estimated by quantitative PCR of extracted DNA from the affected spinal cords were 0.4 to 20 copies/1000 tissue cells, and were well correlated with the numbers of infiltrated CD4 positive cells. From these findings it is suggested that immune responses in the spinal cord of HAM patients gradually change along with the duration of illness in correlation with the decreasing amount of HTLV-I proviral DNA.
HTLV-I infected marmoset lymphocytes lines were established by co-culture with a human HTLV-I infected cell line derived from CSF lymphocytes of a HAM patient, and intravenous auto- or allotransfusion of these cells resulted persistent infection of HTLV-I in common marmosets. The animals show no clinical signs of neurological deficits yet, however, this may become a useful animal model of HTLV-I associated diseases.
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[Publications] S.Ijichi, Shuju Izumo, N.Eiraku, K.Machigashira, R.Kubota, M,Nagai, N.Ikegami, N.Kashio, F.Umehara, I.Maruyama, M.Osame.: "An autoaggressive process against bystander tissues in HTLV-I-infected individuals : a possible pathomechanism of HAM/TSP." Medical Hypotheses. 41. 542-547 (1993)
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