Grant to fund study of role of cytotoxic T cells in HIV neuropathogenesis
Dr. Lydie Trautmann, chief of the cellular immunology lab section for the U.S. Military HIV Research Program (MHRP), and her colleagues from Yale, University of Hawaii and SEARCH Thailand have won a $2.6 million (total over 5 years) grant from the National Institute of Mental Health for a project on the critical role of cytotoxic T cells in HIV neuropathogenesis.
Dr. Trautmann will be co-principal investigator alongside Dr. Serena Spudich of Yale. MHRP’s associate director for therapeutics research, Dr. Jintanat Ananworanich, is also named on the grant.
HIV infects the central nervous system within days of initial exposure and can cause diseases of the nervous tissue despite intervention with antiretroviral therapy (ART). A cytotoxic T cell (CTL) is a white blood cell (lymphocyte) that kills cells infected with HIV.
Infiltration by CTLs into the nervous system is a recognized feature in many neurodegenerative diseases that are associated with neuroinflammation, including multiple sclerosis and Alzheimer’s disease, but their role in HIV neuropathogenesis remains unknown.
The investigators aim to determine the disease-causing mechanisms of CTLs during acute and chronic HIV infection, both prior to and after initiation of ART. To achieve this, they’ll analyze CTLs in the cerebrospinal fluid samples from MHRP’s RV254 acute infection study taking place in Bangkok, Thailand, comparing them to samples from those with chronic HIV infection.
“Understanding the neuropathogenic mechanisms that are established in the first days following exposure and whether they persist with ART is of critical importance to reduce the burden of central nervous system injury among the HIV-infected population,” said Dr. Trautmann. “The results of this study will pave the way for the development of therapeutic strategies to limit CTL-mediated central nervous system damage and preserve cognitive function in HIV-infected patients.”