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Senior Investigator

Steven Jacobson, Ph.D.

Viral Immunology Section

Neuroimmunology and Neurovirology Division
Building 10 Room 5C103
10 Center Drive MSC 1400
Bethesda MD 20892-1400
Office: (301) 496-0519
Lab: (301) 496-0519
Fax: (301) 402-0373

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.

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:

  • The host immune response in HAM/TSP, particularly the role of CD8+, HTLV-I-Tax protein-specific cytotoxic T lymphocytes (CTL).
  • The detection of these immunopathogenic CTL as well as the localization of human retroviral sequences in the central nervous system of HAM/TSP patients.
  • Association of HHV-6 and MS.
  • Development of immunotherapeutic strategies for the treatment of HAM/TSP, including a clinical trial of B-IFN therapy.

Major findings include:

  • 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.
  • The quantitation of HTLV-I DNA in PBL of HAM/TSP patients by real-time Taqman PCR.
  • Identification of altered peptide ligands that have been shown to interfere specifically with antigen-specific CTL clones.
  • 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.

Clinical Protocols

  • Immuno-Virological Evaluation of Human T Cell Leukemia Virus Type-1 Associated Myelopathy (HAM/TSP) ( NCT00001778 )

  • Combined Clinical, Immunological and Virological Assessment of Patients with Multiple Sclerosis (MS) ( NCT00001156 )

  • Human Herpesvirus-6 and Its Effect on the GABA/glutamate Balance in the Cerebrospinal Fluid and in the Brain from Patients with Epilepsy  (NCT00085683 )

Staff Image
  • Nahid Akhyani, B.S.
    Research Assistant
    (301) 402-6391

  • Julie Fortheringham, Ph.D.
    Postdoctoral Fellow

  • Kazunori Fugo, M.D., Ph.D.
    Visiting Fellow

  • Christian Grant, Ph.D.
    Postdoctoral Fellow

  • Steven Jacobson, Ph.D.
    Senior Investigator
    (301) 496-0519

  • Norihiro Takenouchi, M.D., Ph.D.
    Visiting Fellow

  • Oh Unsong, M.D.
    Clinical Fellow

  • Elizabeth Williams, B.S.
    Research Assistant

  • Karen Yao, B.S.
    Predoctoral Fellow

  • 1) Lee NJ, Ha SK, Sati P, Absinta M, Luciano NJ, Lefeuvre JA, Schindler MK, Leibovitch EC, Ryu JK, Petersen MA, Silva AC, Jacobson S, Akassoglou K, Reich DS (2018)
  • Spatiotemporal distribution of fibrinogen in marmoset and human inflammatory demyelination
  • Brain, 141(6), 1637-1649
  • 2) Luciano NJ, Sati P, Nair G, Guy JR, Ha SK, Absinta M, Chiang WY, Leibovitch EC, Jacobson S, Silva AC, Reich DS (2017)
  • Utilizing 3D Printing Technology to Merge MRI with Histology: A Protocol for Brain Sectioning
  • J Vis Exp, 118, e54780
  • 3) Guy JR, Sati P, Leibovitch E, Jacobson S, Silva AC, Reich DS (2016)
  • Custom fit 3D-printed brain holders for comparison of histology with MRI in marmosets
  • J Neurosci Methods, 257, 257:55-63
  • 4) Kubota R, Soldan S, Martin R, and Jacobson S. (InPress) (2013)
  • An altered peptide ligand antagonizes antigen-specific CD8+ CTL in peripheral blood of HAM/TSP patients.
  • J Immunology
  • 5) Oh U, Yamano Y, Mora CA, Ohayon J, Bagnato F, Buttman J, Dambrosia J, Leist T, McFarland HF and Jacobson S (2005)
  • Interferon-ƒÒ1a 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
  • 6) 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
  • 7) 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
  • 8) 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
  • 9) 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
  • 10) 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. Med. , 199, 1367-1377
  • 11) Sundaram R, Rawale SV, Dakappagari NK, Young D, Walker CM, Jacobson S, and Kaumaya PTP (2004)
  • Protective Efficacy of Multiepitope HLA*0201 Restricted CTL Peptide Construct Against Challenge with HTLV-1 Tax Recombinant Vaccinia Virus
  • Acquir Immune Defic Syndr , 37, 1329–1339
  • 12) Monsurro V, Wang E, Yamano Y, Migueles SA, Panelli MC, Smith K, Nagorsen D, Connors M, Jacobson S, and Marincola FM (2004)
  • Quiescent phenotype of tumor-specific CD8+ T cells following immunization
  • Blood, 104, 1970-1978
  • 13) Maloney EM, Nagai M, Hisada M, Soldan SS, Goebel PB, Carrington M, Sawada T, Brennan M, Quinan G, Cranston B, Hanchard B, and Jacobson S (2004)
  • Pre-diagnostic Levels of HTLV-I Proviral Load are Highest in Children who Developed Seborrheic Dermatitis and Severe Anemia in Jamaican
  • J Inf Disease , 189, 41- 45
  • 14) 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
  • 15) Cohen CJ, Sarig O, Yamano Y, Tomaru U, Jacobson S, and Reiter Y (2003)
  • Direct Phenotypic Analysis of human MHC Class I Antigen Presentation: Visualization, Quantitation, and In Situ Detection of Human Viral Epitopes Using Peptide-Specific, MHC-restricted TCR-like Human Recombinant Antibodies
  • Journal of Immunology , 170 (8), 4349-4361
  • 16) Sundaram R, Sun Y, Walker CM, Lemonnier FA, Jacobson S, and Kaumaya PTP (2003)
  • A Novel HTLV-1 Multi-Epitope CTL Peptide Construct Elicits Robust Cellular Immune Responses in HLA-A*0201 Transgenic ƒÒ2M, Db Double Knockout Mice
  • Vaccine, 3808, 1-15
  • 17) Tomaru U, Yamano Y, Nagai M, Maric D, Kaumaya PTP, Biddison WE, and Jacobson S (2003)
  • Detection of virus specific T cells and novel CD8+ T cell epitopes by acquisition of peptide/HLA/GFP complexes
  • Nature Medicine , 9, 469-475
  • 18) Cermelli C, Berti R, Soldan S, Ludwin SK, and Jacobson S (2003)
  • High Frequency of HHV-6 DNA in Multiple Sclerosis Plaques Isolated by Laser Microdissection
  • J Infectious Disease , 187, 1377-1387
  • 19) Puccioni-Sohler M, Chimelli L, Marcon M, Goncalves RR, Pimenta G, Bianco C, Rios M, and Jacobson S (2003)
  • Acute HAM/TSP Complicated With Encephalopathy And Systemic Inflammation
  • Journal of Neurological Sciences , 207, 87-93
  • 20) Grant C, Barmak K, Alefantis T, Yao J, Jacobson S, Wigdahl B (2002)
  • Human T Cell Leukemia Virus Type I and Neurologic Disease: Events in Bone Marrow, Peripheral Blood, and Central Nervous System During Normal Immune Surveillance and Neuroinflammation
  • Journal of Cellular Physiology , 190, 133-159
  • 21) Yamano Y, Nagai M, Brennan B, Mora CA, Soldan SS, Tomaru U, Takenouchi N, Syuji Izumo S, Osame M, and Jacobson S (2002)
  • Real-time quantitative RT-PCR analysis of Human T-cell lymphotropic virus type-I (HTLV-I) tax mRNA: correlation with HTLV-I proviral DNA load, Tax protein expression, Tax specific CD8+ T cell frequency and disease severity in patients with HTLV-I-associat
  • Blood, 99, 88-94
  • 22) Kubota R, Soldan SS, Martin R, and Jacobson S (2002)
  • Selected cytotoxic T lymphocytes with High Specificity for HTLV-I in Cerebrospinal Fluid from a HAM/TSP Patient
  • J NeuroVirol , 8, 53-57
  • 24) Berti R, Brennan MB, Soldan SS, Ohayon JM, Casareto L, McFarland HF, Jacobson S (2002)
  • Increased detection of serum HHV-6 DNA sequences during MS exacerbations and correlation with parameters of multiple sclerosis disease progression
  • J Neurovirol, 8, 252-259
  • 25) Levin MC, Rosenblum MC, Fox CH, and Jacobson S (2001)
  • In Situ Localization of Retrovirus in The Central Nervous System of A Patient Co-infected with HTLV-I and HIV with HAM/TSP and AIDS Dementia Complex
  • J Neurovirol , 7, 6-65
  • 26) Azimi N, Nagai M, Jacobson S, Waldmann TA (2001)
  • Interleukin 15 is an Essential Factor for The Persistence of the Tax-Specific CD8 Cells in HAM/TSP Patients
  • Patients. Proc Natl Acad Sci , 1073, 14559-14564
  • 27) Sakai JA, Nagai M, and Jacobson S (2001)
  • In Vitro Spontaneous Lymphoproliferation in Patients with HTLV-I-Associated Neurological Disease: Predominant Expansion of CD8+ T-cells
  • Blood, 98, 1506-1511
  • 28) Nagai M, Kubota R, Greten TF, Schneck JP, Leist TP, and Jacobson S (2001)
  • Increased Differentiated and Activated HTLV-I Tax11-19-Specific CD8+ Cells in Patients with HTLV-I-Associated Myelopathy / Tropical Spastic Paraparesis: Correlation with HTLV-I Proviral Load
  • J Inf Dis , 183, 197-205
  • 29) Nagai M, Yamano Y, Brennan MB, Mora CA, and Jacobson S (2001)
  • Increased HTLV-I Proviral Load And Preferential Expansion Of HTLV-I Tax-Specific CD8+ T Cells In Cerebrospinal Fluid From Patients With HAM/TSP
  • Annals of Neurology , 50, 807-812
  • 30) Soldan SS, Fogdell-Hahn A, Brennan MB, Mittleman BB, Massacesi L, Seya T, McFarland HF, and Jacobson S (2001)
  • Elevated Serum and CSF Levels of Soluble HHV-6 Cellular Receptor, Membrane Cofactor Protein (MCP; CD46), In Patients with Multiple Sclerosis
  • Annals of Neurology , 50, 486-493
  • 31) Jacobson S and Cross A (2001)
  • Association of Chlamydia pneumoniae and Multiple Sclerosis. Stage Two
  • Neurology , 56, 1128-1129
  • 32) Mayne M, Cheadle C, Soldan SS, Cermelli C, Yamano Y, Akhyani N, Nagel JE, Taub DD, Becker KG, and Jacobson S (2001)
  • Gene Expression Profile of Herpesvirus Infected T cells using Immuno-Microarrays: Upregulation of Pro-Inflammatory Genes
  • J Virol , 75, 11641-11650
  • 33) Nagai M, Brennan MB, Sakai JA, Mora CA, and Jacobson S (2001)
  • CD8+ T cells An in vivo Reservoir for HTLV-I
  • Blood, 98, 1858-1861
  • 34) Kubota R, Soldan S, Martin R, and Jacobson S. (2000)
  • An Altered Peptide Ligand Antagonizes Antigen-Specific CD8+ CTL in Peripheral Blood of HAM/TSP Patients
  • J. Immunol, 164, 5192-5198
  • 35) Cermelli C and Jacobson S (2000)
  • Viruses and Multiple Sclerosis
  • Viral Immunology , 13, 255-267
  • 36) Kubota R, Nagai M, Kawanishi T, Osame M, and Jacobson S (2000)
  • Increased HTLV-I Tax Specific CD8+ Cells in HAM/TSP: Correlation with HTLV-I Proviral Load
  • AIDS Res Hum Retro , 16, 1705-1710
  • 37) Berti R, Soldan S, Akyani N, Leist T, McFarland H, and Jacobson S (2000)
  • Extended Observations on the Association of HHV-6 and MS
  • J. Neurovirol, 6: Suppl 2, S85-S87
  • 38) Akhyani N, Berti R, Brennan M, Soldan SS, Eaton JM, McFarland HF and Jacobson S (2000)
  • . Tissue Distribution and Variant Characterization of HHV-6: Increased Prevalence of HHV-6A in Patients with Multiple Sclerosis
  • J Inf Dis , 182 (5), 1321-1325
  • 39) Soldan SS, Leist TP, Juhng KN, McFarland HF, and Jacobson S. (2000)
  • Increased lymphoproliferative response to HHV-6 A variant in multiple sclerosis patients.
  • Annals of Neurology, 47, 306-313
  • 40) Jacobson S, Soldan SS, Berti R (1998)
  • HHV-6 and Multiple Sclerosis
  • Nature Medicine , (letter)4:538
  • 41) Soldan SS, Berti R, Salem N, Secchiero P, Flamand L, Calabresi P, Brennan MB, Maloni HM, McFarland HF, Lin H, Patnaik M, and Jacobson S. (1998)
  • Association of human herpes virus 6 (HHV-6) with multiple sclerosis: increased IgM response to HHV-6 early antigen and detection of serum HHV-6 DNA.
  • Nature Medicine, 3, 1394-1397
  • 42) Levin MC, Lehky TJ, Flerlage N, Katz D, Kingma DW, Jaffe ES, Heiss JD, Corbet JJ, Patronas N, McFarland HF, and Jacobson S. (1997)
  • Immunopathogenesis of HTLV-I associated chronic progressive neurologic disease: in vivo evidence based on a spinal cord biopsy from a patient with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP)
  • New Eng J Med, 336, 839-845
  • 43) Elovaara I, Koenig, Breweh A, and Jacobson S. (1993)
  • High HTLV-I specific precursor cytotoxic T lymphocyte frequencies in patients with HTLV-I associated neurological disease
  • J Exp Med, 177, 1567-1573
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