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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-08-2477.
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Blood, 15 April 2003, Vol. 101, No. 8, pp. 3074-3081
IMMUNOBIOLOGY
Degenerate specificity of HTLV-1-specific CD8+ T
cells during viral replication in patients with HTLV-1-associated
myelopathy (HAM/TSP)
Ryuji Kubota,
Yoshitaka Furukawa,
Shuji Izumo,
Koichiro Usuku, and
Mitsuhiro Osame
From the Third Department of Internal Medicine, Center
for Chronic Viral Diseases, and Department of Medical Informatics,
Faculty of Medicine, Kagoshima University, Kagoshima,
Japan
Human T-lymphotropic virus type 1 (HTLV-1)-associated
myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurologic disease caused by HTLV-1 infection, in which
HTLV-1-infected CD4+ T cells and HTLV-1-specific
CD8+ T cells may play a role in the disease pathogenesis.
Patients with HAM/TSP have high proviral loads despite vigorous
virus-specific CD8+ T-cell responses; however, it is
unknown whether the T cells are efficient in eliminating the virus in
vivo. To define the dynamics of HTLV-1-specific CD8+
T-cell responses, we investigated longitudinal alterations in HTLV-1
proviral load, amino acid changes in an immunodominant viral epitope,
frequency of HTLV-1-specific T cells, and degeneracy of T-cell
recognition in patients with HAM/TSP. We showed that the frequency and
the degeneracy of the HTLV-1-specific CD8+ T cells
correlated well with proviral load in the longitudinal study. The
proviral load was much higher in a patient with low degeneracy of
HTLV-1-specific T cells compared to that in a patient with comparable
frequency but higher degeneracy of the T cells. Furthermore, in a
larger number of patients divided into 2 groups by the proviral load,
those with high proviral load had lower degeneracy of T-cell
recognition than those with low proviral load. Sequencing analysis
revealed that epitope mutations were remarkably increased in a patient
when the frequency and the degeneracy were at the lowest. These data
suggest that HTLV-1-specific CD8+ T cells with degenerate
specificity are increased during viral replication and control the
viral infection.

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