Cytotoxic T lymphocytes (CTL) have been shown to be important in the clearance of virus infections in experimental animals. There is good correlative evidence that such processes also exist in man, although the definitive experiments have not been performed. In HIV infection, specific CTL responses are present early in infection. However, as patients progress towards arc and AIDS, immune responses become increasingly weak. We will operate under the rationale that the introduction of the CTLs late in disease will be beneficial to the patient. In this developmental project we will devise methods for production of large numbers of MHC restricted, HIV peptide specific cytotoxic T lymphocytes. We will draw on the information acquired in the production of tumor-infiltrating lymphocytes (TIL) in cancer, and will produce lines of cells capable of lysing HIV-autologous AIDS patients. Thus we are proposing to develop the tools for patient-specific autologous immunotherapy. Ultimately this will provide information which will allow us either to confirm or to deny the supposition that CD8+ CTLs are important in the maintenance of a healthy seropositive state, or alternatively are irrelevant or damaging to patients. In addition, it will identify the viral epitopes recognized in vivo.
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