Dr. Nitin Karandikar successfully renewed his VA Merit Award, entitled “Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease.” Based on the outstanding score for the renewal application, Dr. Karandikar was also nominated for and received the VA Senior Clinician Scientist Investigator (SCSI) Award. This SCSI Award includes a MERIT award extension for 4 years, amounting to a total eight-year award.

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 (CNS-CD8) 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" CD8+ T cells are the focus of this grant proposal, which is built around the hypothesis that specific functional and phenotypic subsets of CNS-CD8 form an important and exploitable arm of immune regulation during autoimmune demyelinating disease.  The proposal aims to harness this process for the development of effective immunotherapeutic approaches.  Using the EAE model, the studies will address the fundamental cellular and molecular mechanisms of immune modulation (IFNγ and its receptor, trafficking and cytotoxicity, suppression at the site of pathology) by these autoregulatory CD8 T cells, and will define a potent and enhanceable immune suppressive subset of CNS-CD8. Further, a novel vaccination strategy that reliably engages disease-reversing CNS-CD8 will also be investigated.