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. 1993 Jun 1;177(6):1567–1573. doi: 10.1084/jem.177.6.1567

High human T cell lymphotropic virus type 1 (HTLV-1)-specific precursor cytotoxic T lymphocyte frequencies in patients with HTLV-1-associated neurological disease

PMCID: PMC2191033  PMID: 8496677

Abstract

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.

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Selected References

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  1. Bhigjee A. I., Wiley C. A., Wachsman W., Amenomori T., Pirie D., Bill P. L., Windsor I. HTLV-I-associated myelopathy: clinicopathologic correlation with localization of provirus to spinal cord. Neurology. 1991 Dec;41(12):1990–1992. doi: 10.1212/wnl.41.12.1990. [DOI] [PubMed] [Google Scholar]
  2. Gessain A., Barin F., Vernant J. C., Gout O., Maurs L., Calender A., de Thé G. Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet. 1985 Aug 24;2(8452):407–410. doi: 10.1016/s0140-6736(85)92734-5. [DOI] [PubMed] [Google Scholar]
  3. Gotch F. M., Nixon D. F., Alp N., McMichael A. J., Borysiewicz L. K. High frequency of memory and effector gag specific cytotoxic T lymphocytes in HIV seropositive individuals. Int Immunol. 1990;2(8):707–712. doi: 10.1093/intimm/2.8.707. [DOI] [PubMed] [Google Scholar]
  4. Hoffenbach A., Langlade-Demoyen P., Dadaglio G., Vilmer E., Michel F., Mayaud C., Autran B., Plata F. Unusually high frequencies of HIV-specific cytotoxic T lymphocytes in humans. J Immunol. 1989 Jan 15;142(2):452–462. [PubMed] [Google Scholar]
  5. Jacobson S., Gupta A., Mattson D., Mingioli E., McFarlin D. E. Immunological studies in tropical spastic paraparesis. Ann Neurol. 1990 Feb;27(2):149–156. doi: 10.1002/ana.410270209. [DOI] [PubMed] [Google Scholar]
  6. Jacobson S., Raine C. S., Mingioli E. S., McFarlin D. E. Isolation of an HTLV-1-like retrovirus from patients with tropical spastic paraparesis. Nature. 1988 Feb 11;331(6156):540–543. doi: 10.1038/331540a0. [DOI] [PubMed] [Google Scholar]
  7. Jacobson S., Shida H., McFarlin D. E., Fauci A. S., Koenig S. Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease. Nature. 1990 Nov 15;348(6298):245–248. doi: 10.1038/348245a0. [DOI] [PubMed] [Google Scholar]
  8. Kannagi M., Harada S., Maruyama I., Inoko H., Igarashi H., Kuwashima G., Sato S., Morita M., Kidokoro M., Sugimoto M. Predominant recognition of human T cell leukemia virus type I (HTLV-I) pX gene products by human CD8+ cytotoxic T cells directed against HTLV-I-infected cells. Int Immunol. 1991 Aug;3(8):761–767. doi: 10.1093/intimm/3.8.761. [DOI] [PubMed] [Google Scholar]
  9. Kira J., Itoyama Y., Koyanagi Y., Tateishi J., Kishikawa M., Akizuki S., Kobayashi I., Toki N., Sueishi K., Sato H. Presence of HTLV-I proviral DNA in central nervous system of patients with HTLV-I-associated myelopathy. Ann Neurol. 1992 Jan;31(1):39–45. doi: 10.1002/ana.410310108. [DOI] [PubMed] [Google Scholar]
  10. Koenig S., Fuerst T. R., Wood L. V., Woods R. M., Suzich J. A., Jones G. M., de la Cruz V. F., Davey R. T., Jr, Venkatesan S., Moss B. Mapping the fine specificity of a cytolytic T cell response to HIV-1 nef protein. J Immunol. 1990 Jul 1;145(1):127–135. [PubMed] [Google Scholar]
  11. Koup R. A., Pikora C. A., Luzuriaga K., Brettler D. B., Day E. S., Mazzara G. P., Sullivan J. L. Limiting dilution analysis of cytotoxic T lymphocytes to human immunodeficiency virus gag antigens in infected persons: in vitro quantitation of effector cell populations with p17 and p24 specificities. J Exp Med. 1991 Dec 1;174(6):1593–1600. doi: 10.1084/jem.174.6.1593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Moore G. R., Traugott U., Scheinberg L. C., Raine C. S. Tropical spastic paraparesis: a model of virus-induced, cytotoxic T-cell-mediated demyelination? Ann Neurol. 1989 Oct;26(4):523–530. doi: 10.1002/ana.410260405. [DOI] [PubMed] [Google Scholar]
  13. Osame M., Matsumoto M., Usuku K., Izumo S., Ijichi N., Amitani H., Tara M., Igata A. Chronic progressive myelopathy associated with elevated antibodies to human T-lymphotropic virus type I and adult T-cell leukemialike cells. Ann Neurol. 1987 Feb;21(2):117–122. doi: 10.1002/ana.410210203. [DOI] [PubMed] [Google Scholar]
  14. Parker C. E., Daenke S., Nightingale S., Bangham C. R. Activated, HTLV-1-specific cytotoxic T-lymphocytes are found in healthy seropositives as well as in patients with tropical spastic paraparesis. Virology. 1992 Jun;188(2):628–636. doi: 10.1016/0042-6822(92)90517-s. [DOI] [PubMed] [Google Scholar]
  15. Plata F., Autran B., Martins L. P., Wain-Hobson S., Raphaël M., Mayaud C., Denis M., Guillon J. M., Debré P. AIDS virus-specific cytotoxic T lymphocytes in lung disorders. Nature. 1987 Jul 23;328(6128):348–351. doi: 10.1038/328348a0. [DOI] [PubMed] [Google Scholar]
  16. Plata F., Dadaglio G., Chenciner N., Hoffenbach A., Wain-Hobson S., Michel F., Langlade-Demoyen P. Cytotoxic T lymphocytes in HIV-induced disease: implications for therapy and vaccination. Immunodefic Rev. 1989;1(3):227–246. [PubMed] [Google Scholar]
  17. Román G. C., Osame M. Identity of HTLV-I-associated tropical spastic paraparesis and HTLV-I-associated myelopathy. Lancet. 1988 Mar 19;1(8586):651–651. doi: 10.1016/s0140-6736(88)91452-3. [DOI] [PubMed] [Google Scholar]
  18. Sethi K. K., Näher H., Stroehmann I. Phenotypic heterogeneity of cerebrospinal fluid-derived HIV-specific and HLA-restricted cytotoxic T-cell clones. Nature. 1988 Sep 8;335(6186):178–181. doi: 10.1038/335178a0. [DOI] [PubMed] [Google Scholar]
  19. Shaw G. M., Gonda M. A., Flickinger G. H., Hahn B. H., Gallo R. C., Wong-Staal F. Genomes of evolutionarily divergent members of the human T-cell leukemia virus family (HTLV-I and HTLV-II) are highly conserved, especially in pX. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4544–4548. doi: 10.1073/pnas.81.14.4544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wraith D. C., Smilek D. E., Mitchell D. J., Steinman L., McDevitt H. O. Antigen recognition in autoimmune encephalomyelitis and the potential for peptide-mediated immunotherapy. Cell. 1989 Oct 20;59(2):247–255. doi: 10.1016/0092-8674(89)90287-0. [DOI] [PubMed] [Google Scholar]

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