Proliferation of extra-thymic T cells is also increased which may partially compensate for the thymic defect. These observation supports our efforts toward a therapeutic HIV vaccine targeting Tat protein. HIV-1 Tat is a viral transactivator that increases the rate of viral transcription. Tat also is secreted from infected cells and has immunosuppressive properties affecting T cells. T cells from HIV infected individuals, even at early stages of HIV infection, undergo programmed cell death in response to antigen stimulation.
Tat inhibits proliferation and induces apoptosis in response to an antigen stimulus.
These activities support the notion that Tat may be an ideal vaccine target. This laboratory is now working toward a proof of concept study in macaques to demonstrate the efficacy of this approach as a protective vaccine for uninfected subjects. We have also isolated Tat genes from HIV subtypes common to areas outside of the US and Europe in order to further our immunologic studies and to provide a framework for engineering Tat based vaccines for potential application in Asia and Africa. Our recent studies demonstrate the localization of HIV-Tat and chemokines in CNS tissue from patients with HIV associated CNS disorders. Additional efforts are directed toward the development of chemokine molecules which bind, but do not signal their corresponding receptors.