The immunology and pathogenesis of HIV is being studied in our laboratory by two different approaches. First, cDNA encoding single chain antibody to HIV was used to transfect CD4+ T cells. Stable T cell lines producing intracellular anti-HIV antibody were infected with HIV. Our studies showed that intracellular antibody bound viral antigens, blocked maturation and inhibited viral replication. Specific targeting sequences are now being used to direct the antibody to different compartments of the cell (i.e., cytosol, nucleus, endoplasmic reticulum, transgolgi network and lysosomes). Recently, we extended this project to cytokines and showed that CD4+ T cells, transfected with cDNA encoding interleukin 16 (IL-16), are resistant to HIV infection. The second approach involves studies on the pathogenesis of HIV using transgenic mice expressing a non-infectious HIV construct deficient in gag and pol. These transgenic animals develop a wasting syndrome and die within several weeks after birth. Our studies showed that treatment of these transgenic mice with human chorionic gonadotropin (hCG) inhibits expression of HIV mRNA and protein and prevents wasting and death. Other hormones are now being investigated and their mechanism of action is under study. Our continuing studies on polyreactive antibodies showed that the B cells that make these antibodies have properties consistent with cells that can induce or maintain immunological tolerance. Over the last year we showed that these polyreactive antigen-binding B (PAB) cells are a major component of the B cell repertoire of normal adults and the predominant cell type in the B cell repertoire of the newborn. The function of this major B cell subtype is being pursued.
