application): The overall goal of the application is to examine the feasibility of reconstitution of HCMV immunity in HIV-infected patients by adoptive transfer of autologous in vitro expanded CD8+ HCMV-specific cytotoxic T lymphocytes (CTL) and CD4+ HCMV-specific Th clones which will be genetically modified to resist infection with HIV. The adoptive transfer of HCMV-specific CD8+ and CD4+ T-cell clones has already been used successfully by the applicants to restore protective levels of immunity in immunodeficient bone marrow transplant recipients. Besides adoptive transfer of HCMV-specific T cells, an important part of the proposed studies will be to determine whether prospective immunologic and virologic monitoring of AIDS patients can be used to identify individuals who are at high risk for HCMV disease.
The specific aims of the proposed studies are: (1) to determine whether concurrent immunologic and virologic monitoring can identify patients with AIDS at high risk for development of HCMV disease; (2) to evaluate the safety, in vivo persistence and antiviral activity of adoptively transferred CD8+ HCMV-specific CTL clones in HIV-infected patients; and (3) to evaluate the safety, in vivo persistence and immunomodulatory function of adoptively transferred CD4+ HCMV-specific Th clones genetically modified to resist HIV infection.
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