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| Steven Jacobson, Ph.D., Senior Investigator |
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Dr. Jacobson received his B.A. from Temple University and his Ph.D. from the Rennselear Polytechnic Institute where he earned his degree in Virology. The focus of his research was on persistent virus infections. In 1981, Dr. Jacobson joined the Neuroimmunology Branch as a postdoctoral research fellow in immunology as a National Multiple Sclerosis Society Fellow. In 1993, he received tenure and formed the Viral Immunology Section to study the role of human viruses in the pathogenesis of chronic progressive neurologic disease. Dr. Jacobson's laboratory is studying virological, immunological, and molecular mechanisms associated with the human T lymphotropic virus type-I associated myelopathy/tropical spastic paraparesis and the association of virus in multiple sclerosis.
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Staff:
- Nahid Akhyani, B.S., Research Assistant, (301) 402-6391 akhyanin@ninds.nih.gov
- Julie Fortheringham, Ph.D., Postdoctoral Fellow fotherij@ninds.nih.gov
- Kazunori Fugo, M.D., Ph.D., Visiting Fellow fugok@ninds.nih.gov
- Christian Grant, Ph.D., Postdoctoral Fellow grantchr@ninds.nih.gov
- Steven Jacobson, Ph.D., Senior Investigator, (301) 496-0519 stevej@helix.nih.gov
- Norihiro Takenouchi, M.D., Ph.D., Visiting Fellow takenoun@ninds.nih.gov
- Oh Unsong, M.D., Clinical Fellow ohu@ninds.nih.gov
- Elizabeth Williams, B.S., Research Assistant williamse@ninds.nih.gov
- Karen Yao, B.S., Predoctoral Fellow yaok@ninds.nih.gov
Research Interests:
Human T lymphotropic virus type I (HTLV-I) is associated with a chronic progressive neurological disorder known as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease clinically similar to the chronic progressive form of multiple sclerosis (MS). Other viruses such as human herpes virus type 6 (HHV-6) have been associated with MS. An understanding of the pathogenesis of a neurologic disease with a known viral etiology will aid in defining similar mechanisms of pathogenesis in MS, a disease of unknown etiology.
Areas of research addressing these neurovirological and neuroimmunological issues include:
o The host immune response in HAM/TSP, particularly the role of CD8+, HTLV-I-Tax protein-specific cytotoxic T lymphocytes (CTL).
o The detection of these immunopathogenic CTL as well as the localization of human retroviral sequences in the central nervous system of HAM/TSP patients.
o Association of HHV-6 and MS.
o Development of immunotherapeutic strategies for the treatment of HAM/TSP, including a clinical trial of B-IFN therapy.
Major findings include:
o The demonstration of spontaneous proliferation of CD4+ and CD8+ cells from HAM/TSP patients ex vivo, including Tax-specific CD8+ CTL directly isolated from PBL of HAM/TSP patients.
o The quantitation of HTLV-I DNA in PBL of HAM/TSP patients by real-time Taqman PCR.
o Identification of altered peptide ligands that have been shown to interfere specifically with antigen-specific CTL clones.
o Association of HHV-6 and MS based on increased IgM response to HHV-6 early antigen, detection of HHV-6 DNA in sera from MS patients, and the observation of an increased proliferative response to the HHV-6A variant in MS patients.
Collectively, these results continue to define the role of human viruses in chronic progressive neurologic disease.
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Clinical Protocols:
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Immuno-Virological Evaluation of Human T Cell Leukemia Virus Type-1 Associated Myelopathy (HAM/TSP) (
NCT00001778 )
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Combined Clinical, Immunological and Virological Assessment of Patients with Multiple Sclerosis (MS) (
NCT00001156 )
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Human Herpesvirus-6 and Its Effect on the GABA/glutamate Balance in the Cerebrospinal Fluid and in the Brain from Patients with Epilepsy (
NCT00085683 )
Selected Recent Publications:
Yamano Y, Takenouchi N, Chris Grant, Li H-C, Tomaru U, Yao K, Maric D, and Jacobson S (2005) Human T-cell lymphotropic virus type I (HTLV-I) induced dysfunction of CD4+CD25+ T cells breaks immunological self-tolerance in patients with HTLV-I associated neurological disease, J Clin Invest 115, 1361-1368.
Oh U, Yamano Y, Mora CA, Ohayon J, Bagnato F, Buttman J, Dambrosia J, Leist T, McFarland HF and Jacobson S (2005) Interferon-��1a therapy for HTLV-I-associated Myelopathy / Tropical Spastic Paraparesis (HAM/TSP) Reduces HTLV-I-specific CD8+ T cells: Analysis of HAM/TSP biomarkers, Annals of Neurology 57, 526-534.
R Cassiani-Ingoni, H Greenstone, D Donati, A Fogdell-Hahn, E Martinelli, D Refai, R Martin, EA Berger and S Jacobson (2005) Viral infection induces cell-cell fusion of human lymphocytes with oligodendrocytes through CD46, Glia.
Semmes OJ, Cazares L, Ward M, Moody M, Bray S, Maloney E, Kisada M, Wright GL, Gygi S and Jacobson S (2005) Discrete Protein Signatures Discriminate between Adult T-cell Leukemia and HTLV-1-Associated Myelopathy , Leukemia 19 (7), 1229-1238.
Yoshihisa Y, Cohen CJ, Tomaru U, Li HC, Takenouchi N, Biddison WE, Reiter Y, and Jacobson S (2004) Increased expression of HTLV-I Tax11-19 peptide/HLA-A*201 complexes on CD4+CD25+ T cells detected by TCR-like antibody in HAM/TSP patients, J. Exp. 199, 1367-1377.
Donati D, Ahkyani N, Fogdell-Hahn A, Cermelli C, Vortmeyer A, Heiss JD, P. Cogen P, Gaillard WD, Sato S, Theodore WH, and Jacobson S (2003) Detection of Human Herpesvirus 6 (HHV-6) in Mesial Temporal Lobe Epilepsy Surgical Brain Resections, Neurology 61, 1405-1411.
Full Text/Abstract
All Selected Publications
Contact Information:
Dr. Steven Jacobson
Viral Immunology Section
Neuroimmunology Branch, NINDS
Building 10, Room 5N-214
10 Center Drive, MSC 1400
Bethesda, MD 20892-1400
Telephone: (301) 496-0519 (office),
(301) 496-0519 (laboratory),
(301) 402-0373 (fax)
Email: jacobsons@ninds.nih.gov
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