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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2411-2420.
Prepublished online as a Blood First Edition Paper on May 23, 2008May 27, 2008; DOI 10.1182/blood-2008-02-140335.
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Submitted February 21, 2008
Accepted April 24, 2008
Impaired function of human T lymphotropic virus type 1 (HTLV-1) specific CD8+ T cells in HTLV-1-associated neurological disease
Amir H Sabouri, Koichiro Usuku, Daisuke Hayashi, Shuji Izumo, Yoshiro Ohara, Mitsuhiro Osame, and Mineki Saito*
Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Department of Medical Information Technology and Administration Planning, Kumamoto University Hospital, Kumamoto, Japan
Center for Chronic Viral Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Department of Microbiology, Kanazawa Medical University, Kanazawa, Japan
* Corresponding author; email: mineki{at}kanazawa-med.ac.jp.
Despite abundant activated virus-specific cytotoxic T lymphocytes (CTLs), patients with human T lymphotropic virus type 1 (HTLV-1) associated myelopathy/ tropical spastic paraparesis (HAM/TSP) showed a significantly higher frequency of infected T cells than healthy virus carriers (HCs). Here, we demonstrated that at a given proviral load, the frequency of CD8+ T cells that are negative for specific costimulatory molecules was significantly higher in HAM/TSP than age-matched HCs and uninfected normal controls (NCs), whereas the frequency of intracellular perforin positive CD8+ T cells was significantly lower in both HAM/TSP and HCs than NCs. An inverse correlation between HTLV-1 proviral load (PVL) and % perforin+CD8+ T cells were observed only in disease protective allele HLA-A*02 positive HCs, but not in HAM/TSP patients, whether HLA-A*02 positive or negative, nor in HLA-A*02 negative HCs. Significantly lower perforin expression was observed in HTLV-1-specific than cytomegalovirus-specific CD8+ T cells. Majority of HTLV-1-specific CD8+ T cells in HCs showed a CD28-CD27+ phenotype whereas HAM/TSP showed a CD28-CD27- phenotype. HTLV-1-specific CD8+ T cells from HAM/TSP patients showed significantly lower degranulation than HCs by CD107a mobilization assay. These findings suggest that an impaired function of HTLV-1 specific CTLs is associated with failing antiviral control and disease HAM/TSP.
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