Severe loss of invariant NKT cells exhibiting anti-HTLV-1 activity in patients with HTLV-1-associated disorders.
Invariant natural killer T (iNKT) cells are unique T cells that regulate the immune response to microbes, cancers, and autoimmunity. We assessed the characteristics of iNKT cells from persons infected with human T-lymphotropic virus type 1 (HTLV-1). Whereas most infected persons remain asymptomatic carriers (ACs) throughout their lives, a small proportion, usually with high equilibrium proviral loads,develop 2 diseases: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia (ATL). We demonstrated that the frequency of iNKT, NK, and dendritic cells in the peripheral blood of HAM/TSP and ATL patients is decreased. We also observed an inverse correlation between the iNKT cell frequency and the HTLV-1 proviral load in the peripheral blood of infected persons. Notably, in vitro stimulation of peripheral blood cells with alpha-galactosylceramide led to an increase in the iNKT cell number and a subsequent decrease in the HTLV-1-infected T-cell number in samples from ACs but not HAM/TSP or ATL patients. Our results suggest that iNKT cells contribute to the immune defense against HTLV-1, and iNKT-cell depletion plays an important role in the pathogenesis of HAM/TSP and ATL. Therefore, iNKT cell-based immunotherapy may be an effective strategy for preventing these HTLV-1-associated disorders.
Azakami
Kazuko
K
Department of Molecular Medical Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan.
Sato
Tomoo
T
Araya
Natsumi
N
Utsunomiya
Atae
A
Kubota
Ryuji
R
Suzuki
Kenshi
K
Hasegawa
Daisuke
D
Izumi
Toshihiko
T
Fujita
Hidetoshi
H
Aratani
Satoko
S
Fujii
Ryoji
R
Yagishita
Naoko
N
Kamijuku
Hajime
H
Kanekura
Takuro
T
Seino
Ken-ichiro
K
Nishioka
Kusuki
K
Nakajima
Toshihiro
T
Yamano
Yoshihisa
Y
D019264:Adoptive Transfer; D000328:Adult; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000276:immunology* / Q000628:therapy; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D015493:Paraparesis, Tropical Spastic / Q000097:blood / Q000276:immunology* / Q000628:therapy; D019562:Viral Load
D005699:Galactosylceramides