Steven Jacobson, Ph.D.

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.

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.