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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-08-2477.
Submitted August 19, 2002
Accepted December 2, 2002
Degenerate specificity of HTLV-I-specific CD8+ T cells during viral replication in patients with HTLV-I-associated myelopathy (HAM/TSP)
Ryuji Kubota*, Yoshitaka Furukawa, Shuji Izumo, Koichiro Usuku, and Mitsuhiro Osame
The Third Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
Department of Medical Informatics, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
* Corresponding author; email: kubotar{at}m2.kufm.kagoshima-u.ac.jp.
Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurological disease caused by HTLV-I infection, in which HTLV-I-infected CD4+ T cells and HTLV-I-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-I-specific CD8+ T cell responses, we have investigated longitudinal alterations in HTLV-I proviral load, amino acid changes in an immunodominant viral epitope, frequency of HTLV-I-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-I-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-I-specific T cells, compared to a patient with comparable frequency but higher degeneracy of the T cells. Furthermore, in a larger number of patients divided into two 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 degeneracy were at the lowest. These data suggest that HTLV-I-specific CD8+ T cells with degenerate specificity are increased during viral replication, and control the viral infection.
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