Jonathan Kipnis, Ph.D.

Assistant Professor University of Nebraska Medical Center, Department of Pharmacology and Ophthalmology Phone (402) 559-4074 Fax: (402) 559-7495 E-mail: jkipnis@unmc.edu

Research Interests

Our laboratory explores neuro-immune interactions under normal physiological and pathological conditions. It was recently found that T cells (players of the adaptive arm of the immune system) are important players in a spontaneous response to CNS injury. Autoimmune T cells, the same cells that can induce autoimmune disease, can also protect injured neurons, if well controlled.

Naturally occurring regulatory CD4+CD25+ T cells were found to control this beneficial immune response to CNS injury. One of the aspects studied in our laboratory is the biology of these regulatory T cells and their interaction with other T cells and with neural cells.

Recently, it was proposed that T cells might not only have a role in protecting the injured neurons, but also in supporting cognitive functions. Immune deficient mice showed significantly reduced cognitive abilities when compared to mice with a normal immune system. Reconstitution of the immune system in immune-deficient mice improved their cognition. Currently, we try to apply this knowledge to the development of a vaccine for cognitive disorders associated with reduced immune activity (e.g. HIV-associated dementia).

Boost of the immune activity was also shown to protect brain from cognitive decline associated with psychotic behavior, reminiscent of schizophrenia. These results led to interesting discoveries of potential vaccines for mental disorders.

Regeneration of CNS tissue is very limited. In late 90’s it was shown that immune system boosts regeneration of injured spinal cord. In our laboratory, we try to regenerate damaged retina using rodent embryonic progenitor cells via boost of immune activity.

We work with live animals and cultured cells from mice, rats and human origins. Our main techniques are in molecular and cellular biology, immunology, neurobiology, cell and tissue culture, animal behavior, in-vivo models of neurodegenerative and mental disorders and tissue histology.

Long-range Goals

• Naturally occurring regulatory CD4+CD25+ T cells as an evolutionary compromise between a “need” and a “risk” of autoimmunity

• Immune system – a new player in brain cognition

• Antipsychotic immunity – role of immune system in mental disorders

• Regeneration of non-regenerative tissue – building new “vision”

Techniques used in the Laboratory

• Live animals and cultured cells from mice, rats and human origins.

• Molecular and cellular biology: PCR, real-time PCR, Western blots, immuno-precipitations, etc.

• Immunology: Cell isolations, MACSorting, FACSorting, FACS analysis, cell culture

• Neurobiology: Rodent neurosurgeries and other animal models for neurodegenerative disorders, work with rodent neural tissue, rodent and human tissue histology, rodent and human neural cell cultures (including neural stem cells from rodents)Immunohistochemistry, animal behavior models for mental and cognitive disorders).

Representative Publications

• Kipnis, J., Avidan, H., Caspi, R. R. & Schwartz, M. Dual effect of CD4+CD25+ regulatory T cells in neurodegeneration: A dialogue with microglia. Proc Natl Acad Sci U S A (2004).

• Kipnis, J. et al. Dopamine, through the extracellular signal-regulated kinase pathway, downregulates CD4+CD25+ regulatory T-cell activity: implications for neurodegeneration. J Neurosci 24, 6133-43 (2004).

• Kipnis, J., Cohen, H., Cardon, M., Ziv, Y. & Schwartz, M. T cell deficiency leads to cognitive dysfunction: implications for therapeutic vaccination for schizophrenia and other psychiatric conditions. Proc Natl Acad Sci U S A 101, 8180-5 (2004).

• Kipnis, J. et al. Neuroprotective autoimmunity: naturally occurring CD4+CD25+ regulatory T cells suppress the ability to withstand injury to the central nervous system. Proc Natl Acad Sci U S A 99, 15620-5. (2002).

• Kipnis, J. & Schwartz, M. Dual action of glatiramer acetate (Cop-1) in the treatment of CNS autoimmune and neurodegenerative disorders. Trends Mol Med 8, 319-23. (2002).