A novel approach in the immunotherapy of AIDS (Immune deficiency)

A novel approach to the immunotherapy of AIDS involving the use of semi-allogeneic cell hybrids is detailed in this dissertation. This approach involves the use of semi-allogeneic cell hybrids generated from the fusion of peripheral blood mononuclear cells (PBMC) derived from HIV-positive individuals with a designated cell line, FO 1–12. The objective of this study was to test PBMC exposed in vitro to semi-allogeneic cell hybrids derived from the same HIV-infected individual to determine if a specific cytotoxic response could be developed against cells expressing the HLA-A2-restricted, HIV-derived antigenic determinant, GAG. Stimulation experiments were conducted on PBMC from selected HLA-A2-positive, HIV-infected individuals. Following two-week stimulation, in the presence of IL-2 and exogenous GAG peptide with or without irradiated semi-allogeneic cell hybrids, effector cells were harvested and subjected to testing by cytotoxicity assays and tetramer analyses. The results of these studies consistently demonstrated that PBMC stimulated in the presence of GAG peptide and semi-allogeneic cell hybrids exhibit greater antigen-specific cytolytic activity than PBMC stimulated with only exogenous peptide. This novel approach may foster clinical studies utilizing semi-allogeneic cell hybrids as adjuvant immunotherapy against HIV.; Our studies on semi-allogeneic cell hybrids also allowed us to explore the possibility of cross-recognition between HLA-A2-restricted viral epitopes. It has been reported that the matrix protein of the influenza A virus and the matrix and capsid proteins of HIV-1 share structural similarities, which may be of evolutionary and biological significance. Here, we report evidence of cross-recognition between the influenza A-derived FLU-M1_58–66 and HIV-1 p17 GAG_77–85 epitopes following in vitro stimulation of PBMC derived from either HIV-infected or uninfected HLA-A2-positive donors. This conclusion is supported by cytotoxicity studies, tetramer analyses, cytokine-release assays and molecular studies on the β-chain gene of the T-cell receptor (TCR). These experimental results suggest that immunity to structural components of the influenza virus may drive a specific immune response to structural components of HIV in both infected and uninfected individuals.