PMID- 14734756 OWN - NLM STAT- MEDLINE DCOM- 20040507 LR - 20190516 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 172 IP - 3 DP - 2004 Feb 1 TI - Human T cell lymphotropic virus type I (HTLV-I)-specific CD4+ T cells: immunodominance hierarchy and preferential infection with HTLV-I. PG - 1735-43 AB - CD4(+) T cells predominate in early lesions in the CNS in the inflammatory disease human lymphotropic T cell virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), but the pathogenesis of the disease remains unclear and the HTLV-I-specific CD4(+) T cell response has been little studied. We quantified the IFN-gamma-producing HTLV-I-specific CD4(+) T cells, in patients with HAM/TSP and in asymptomatic carriers with high proviral load, to test two hypotheses: that HAM/TSP patients and asymptomatic HTLV-I carriers with a similar proviral load differ in the immunodominance hierarchy or the total frequency of specific CD4(+) T cells, and that HTLV-I-specific CD4(+) T cells are preferentially infected with HTLV-I. The strongest CD4(+) T cell response in both HAM/TSP patients and asymptomatic carriers was specific to Env. This contrasts with the immunodominance of Tax in the HTLV-I-specific CD8(+) T cell response. The median frequency of HTLV-I-specific IFN-gamma(+) CD4(+) T cells was 25-fold greater in patients with HAM/TSP (p = 0.0023, Mann-Whitney) than in asymptomatic HTLV-I carriers with a similar proviral load. Furthermore, the frequency of CD4(+) T cells infected with HTLV-I (expressing Tax protein) was significantly greater (p = 0.0152, Mann-Whitney) among HTLV-I-specific cells than CMV-specific cells. These data were confirmed by quantitative PCR for HTLV-I DNA. We conclude that the high frequency of specific CD4(+) T cells was associated with the disease HAM/TSP, and did not simply reflect the higher proviral load that is usually found in HAM/TSP patients. Finally, we conclude that HTLV-I-specific CD4(+) T cells are preferentially infected with HTLV-I. FAU - Goon, Peter K C AU - Goon PK AD - Department of Immunology, Imperial College London, London, United Kingdom. FAU - Igakura, Tadahiko AU - Igakura T FAU - Hanon, Emmanuel AU - Hanon E FAU - Mosley, Angelina J AU - Mosley AJ FAU - Barfield, Anna AU - Barfield A FAU - Barnard, Amanda L AU - Barnard AL FAU - Kaftantzi, Lambrini AU - Kaftantzi L FAU - Tanaka, Yuetsu AU - Tanaka Y FAU - Taylor, Graham P AU - Taylor GP FAU - Weber, Jonathan N AU - Weber JN FAU - Bangham, Charles R M AU - Bangham CR LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (Gene Products, env) RN - 0 (Gene Products, tax) RN - 0 (Immunodominant Epitopes) SB - IM MH - Amino Acid Sequence MH - CD4-Positive T-Lymphocytes/*immunology/pathology/*virology MH - CD8-Positive T-Lymphocytes/immunology/virology MH - Carrier State/immunology/pathology/virology MH - Cytomegalovirus/immunology MH - Cytotoxicity, Immunologic MH - Epitope Mapping MH - Epitopes, T-Lymphocyte/*immunology MH - Gene Products, env/immunology MH - Gene Products, tax/immunology MH - HTLV-I Infections/*immunology/pathology/virology MH - Human T-lymphotropic virus 1/*immunology MH - Humans MH - Immunodominant Epitopes/*immunology MH - Lymphocyte Count MH - Molecular Sequence Data MH - Paraparesis, Tropical Spastic/immunology/pathology/virology MH - Proviruses/immunology MH - Viral Load EDAT- 2004/01/22 05:00 MHDA- 2004/05/08 05:00 CRDT- 2004/01/22 05:00 PHST- 2004/01/22 05:00 [pubmed] PHST- 2004/05/08 05:00 [medline] PHST- 2004/01/22 05:00 [entrez] AID - 10.4049/jimmunol.172.3.1735 [doi] PST - ppublish SO - J Immunol. 2004 Feb 1;172(3):1735-43. doi: 10.4049/jimmunol.172.3.1735.