High human T cell lymphotropic virus type 1 (HTLV-1)-specific precursor cytotoxic T lymphocyte frequencies in patients with HTLV-1-associated neurological disease.
The frequencies of human T cell lymphotropic virus type 1 (HTLV-1)-specific CD8+ precursor cytotoxic T lymphocytes (pCTL) were quantitated from lymphocytes obtained from the peripheral blood and cerebrospinal fluid (CSF) of infected individuals with and without HTLV-1-associated neurological disease. An estimate of the pCTL was obtained by separating CD8+ cells, plating these cells in limiting dilution, and testing wells for HTLV-1 specific lysis. Targets consisted of autologous lymphoblastoid cell lines (LCL) infected with vaccinia constructs expressing HTLV-1 gene products or LCL pulsed with HTLV-1 synthetic peptides. In patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), the frequency of HTLV-1 p40X-specific pCTL was at least 40-280-fold higher than in asymptomatic HTLV-1-infected individuals. All HAM/TSP patients (five of five) predominantly recognized HTLV-1 products encoded within the pX region. Lower pCTL to env were demonstrated in three patients, and only one of five HAM/TSP patients had pCTL to gag. A synthetic peptide corresponding to the tax region of HTLV-1 (peptide 11-19, amino acid sequence LLFGYPVYV) was recognized in association with human histocompatibility leukocyte antigen (HLA)-A2 in two HLA-A2 HAM/TSP patients with a high CD8+ pCTL frequency of 1/325 and 1/265, respectively. A second immunodominant region of HTLV-1 tax (peptide 90-55, amino acid sequence VPYKRIEEL) was identified to be restricted by HLA-B14 in two HLA-B14 HAM/TSP patients with a CD8+ pCTL frequency of 1/640 and 1/1,125, respectively. Lymphocytes from the CSF of a patient with HAM/TSP also showed a pCTL frequency against p40X of similar magnitude to that demonstrated from peripheral blood lymphocytes (PBL). The HLA-A2-mediated CSF pCTL activity to the immunodominant tax-specific peptide 11-19 was also comparable to pCTL from PBL. These results indicate that an extremely high pCTL frequency to HTLV-1 tax-encoded peptides may be related to pathogenesis of myeloneuropathy associated with HTLV-1.
Neuroimmunology Branch, National Institutes of Health, Bethesda, Maryland 20892.
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Elovaara
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Koenig
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Brewah
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Woods
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Lehky
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Jacobson
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D016827:CD8 Antigens / Q000032:analysis; D002555:Cerebrospinal Fluid / Q000166:cytology; D005260:Female; D016356:Gene Products, tax / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015493:Paraparesis, Tropical Spastic / Q000134:cerebrospinal fluid / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
D016827:CD8 Antigens; D016356:Gene Products, tax; D010446:Peptide Fragments