Decreased human T lymphotropic virus type I (HTLV-I) provirus load and alteration in T cell phenotype after interferon-alpha therapy for HTLV-I-associated myelopathy/tropical spastic paraparesis.
To analyze the mechanism by which interferon (IFN)-alpha is effective against human T cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), we investigated the T cell phenotype and HTLV-I provirus load in peripheral blood mononuclear cells from 25 patients with HAM/TSP that were obtained before and after administration of IFN-alpha. The frequency of memory (CD45RA(-)CD27(+)) T cells that were CD8(high+), CXCR3(+) cell populations, and HTLV-I provirus loads were significantly decreased after treatment. The proportion of memory T cells in the CD8(high+) cell population correlated well with HTLV-I provirus load, whereas the proportion of effector (CD45RA(+)CD27(-)) cells in the CD8(high+) cell population was inversely correlated with provirus load. Interestingly, the frequency of perforin expression in CD8(high+) cells was significantly decreased after treatment in patients who experienced clinical improvement, whereas patients who did not experience clinical improvement showed an increased frequency of perforin expression. Our data suggest that fluctuations in these cell subsets are associated with both the immunomodulatory effect of IFN-alpha and the observed clinical benefit of IFN-alpha treatment in patients with HAM/TSP.
Saito
Mineki
M
Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima, Japan. mineki@m3.kufm.kagoshima-u.ac.jp.
Nakagawa
Masanori
M
Kaseda
Shun
S
Matsuzaki
Toshio
T
Jonosono
Manabu
M
Eiraku
Nobutaka
N
Kubota
Ryuji
R
Takenouchi
Norihiro
N
Nagai
Masahiro
M
Furukawa
Yoshitaka
Y
Usuku
Koichiro
K
Izumo
Shuji
S
Osame
Mitsuhiro
M
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification*; D006801:Humans; D007156:Immunologic Memory; D007273:Injections, Intramuscular; D016898:Interferon-alpha / Q000627:therapeutic use*; D017493:Leukocyte Common Antigens / Q000032:analysis; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011533:Proviruses / Q000302:isolation & purification*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis; D019562:Viral Load
D000276:Adjuvants, Immunologic; D016827:CD8 Antigens; C515187:CXCR3 protein, human; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D054353:Perforin; D017493:Leukocyte Common Antigens