Dr. Nitin Karandikar received a four-year VA Merit Award, entitled “Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease.”
Dr. Karandikar's research focuses on the immune processes that underlie the causation and regulation of multiple sclerosis, an inflammatory demyelinating disease of the central nervous system (CNS). Through studies in human MS as well as its animal model (called EAE), his group was the first to show that CD8+ T cells that are targeted against CNS antigens had the unexpected effect of suppressing disease. His group also was the first to show that CD8+ T cells are responsible for mediating the therapeutic effect of glatiramer acetate, a commonly used treatment for MS.
These novel "autoregulatory" and therapy-induced CD8+ T cells are a focus of this grant proposal. Using the EAE model, the studies will dissect the mechanisms by which CNS-specific CD8+ T cells might regulate the immune system to suppress demyelinating disease, aiming to understand the various cellular and molecular interactions required to achieve this effect. This knowledge will then be used for the preclinical testing of a novel immunotherapeutic strategy for this disease.
In studies published recently in Nature's Scientific Reports, Dr. Karandikar's laboratory showed that a vaccination/infection approach (using engineered Listeria monocytogenes) could be used to induce autoregulatory CD8+ T cells and thereby suppress disease. These complimentary studies will also be pursued separately in the lab.