A rat model of HTLV-I infection: development of chronic progressive myeloneuropathy in seropositive WKAH rats and related apoptosis.
In seropositive HTLV-I carrier rats of the WKAH strain inoculated with 2 x 10(7) MT-2 cells at 3-6 months of age, chronic progressive myeloneuropathy, tentatively designated as HTLV-I-associated myelopathy (HAM) rat disease, occurred when the rats were 19-23 months old. Clinical and pathological findings were basically identical to those of seronegative HAM rats of the same strain neonatally inoculated with MT-2 cells. It appears that a high dose of MT-2 cells (10(8) cells) is more effective for the induction and acceleration of HAM rat disease. Seronegative and seropositive carriers of other strains (F344, ACI, and LEW), WKAH rats inoculated with HUT-78 (a human T cell line without HTLV-I infection), and untreated WKAH rats at comparable ages did not develop HAM rat disease, thereby indicating that development of this disease is caused by HTLV-I infection and is under strict genetic restriction of the host strain. Chronological examination of HAM rat disease induced by 10(7) MT-2 inoculation into newborn rats showed that the spinal cord lesion began to develop by 12 months of age. T cells were absent in the affected spinal cord throughout the disease process. There was morphological evidence of apoptotic death of oligodendrocytes in the affected spinal cord. Apoptosis was also confirmed by the specific nick end labeling of the nuclear fragmentation in situ, and the apoptotic oligodendrocytes confined to the demyelinating foci, and the number of apoptotic cells positively correlated with severity of the spinal cord lesion.(ABSTRACT TRUNCATED AT 250 WORDS)
Seto
K
K
Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
Abe
M
M
Ohya
O
O
Itakura
O
O
Ishiguro
N
N
Ikeda
H
H
Wakisaka
A
A
Yoshiki
T
T
D000818:Animals; D017209:Apoptosis; D002353:Carrier State / Q000821:virology; D002460:Cell Line; D004279:DNA, Viral / Q000378:metabolism; D005260:Female; D015481:HTLV-I Antibodies / Q000032:analysis; D015490:HTLV-I Infections / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016253:Microscopy, Immunoelectron; D009132:Muscles / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D009836:Oligodendroglia / Q000502:physiology; D016133:Polymerase Chain Reaction; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology* / Q000821:virology
D004279:DNA, Viral; D015481:HTLV-I Antibodies