This SPIRAT Program is a focused multifrontal attack on HIV using the cellular immune system as its weapon. It will develop a concerted approach, building upon well-focused laboratory and primate experiments, to design and implement small pilot trials to treat infected patients with adoptively transferred expanded viral-specific and nonspecific T lymphocytes and with cytokines that stimulate T cell immunity and with agents that block the activity of proinflammatory cytokines. The heart of the Program are 3 projects whose goals are to explore and optimize the use of viral-specific CD8 cytotoxic T cells (CTL) with and without cytokine therapy (Project 1, Judy Lieberman, Hematology Oncology, New England Medical Center), the expansion of both nonspecific and antigen-specific CD4 T cells especially in patients with advanced disease (Project 2, Bruce Walker and Paul Johnson, Massachusetts General Hospital and the New England Primate Center), and the use of cytokines that support the elaboration of T cell immunity, such as IL12 and IL2, as well as of agents that specifically bind and block the action of the proinflammatory cytokines IL1 and TNF (Project 2, Paul Skolnik and Charles Dinarello, Geographic Medicine and Infectious Diseases, New England Medical Center). Both in vitro laboratory work as well as primate studies in the SIV-macaque model will be used to gain information essential to the thoughtful use of these therapeutic modalities, initially alone and then in combination. Core laboratories will provide valuable assistance to the projects for HIV viral sequencing, peptide synthesis and cytokine measurement.
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