Mechanisms of protective immunity in response to virulent encephalitic viruses such as Venezuelan Equine Encephalitis Virus (VEEV) are not fully elucidated. Serum neutralizing antibodies are an important component of the host response to vaccination and infection and appear to play a role in the control of peripheral infection but not in control of the virus in the central nervous system (CNS). The role of both helper, cytotoxic and gamma delta T cell receptor (TCR)-bearing cells is also under investigation. Adoptive transfer and loss of function studies in mice have demonstrated a key role for CD4⁺ T cells in preventing the development of lethal encephalitis.