Playroom in the outpatient clinic.
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Biomedical subjects
Publications and source records attributed to E G Engleman.
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In independent studies, 51% and 36% of patients with rheumatoid arthritis have been shown to possess HLA-Dw4 compared to 7% and 13% of controls. In one study Dw4 positive patients more frequently had rheumatoid factor in their sera than did Dw4 negative patients. In order to determine if the Dw4 specificity is associated with the disease or with the presence of rheumatoid factor, the frequency of this HLA antigen has been determined in 24 healthy women known to have rheumatoid factor (median titer 1:160). Only 3 were found to have the Dw4 specificity, suggesting that this specificity is not associated with rheumatoid factor in the absence of rheumatoid arthritis.
Formation of syncytia, with progression to cell death, is a characteristic feature of in vitro cultures of susceptible cells infected with human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). Viral antigen-positive multinucleated giant cells have also been observed in histological sections from infected individuals. In vitro, formation of these multinucleated giant cells occurs through cell fusion which is dependent on cell-surface expression of the differentiation antigen CD4. Utilizing a recombinant vaccinia virus containing the gene for the envelope glycoprotein of HTLV-III/LAV, we demonstrate that cell-surface expression of this protein, in the absence of other HTLV-III/LAV structural or regulatory proteins, is sufficient to induce CD4-dependent cell fusion, leading to cell death, one of the characteristic manifestations of AIDS (acquired immune deficiency syndrome) virus cytopathology. This process may contribute to the loss of CD4+ T cells seen in AIDS.
Dendritic cells (DC) are potent antigen-presenting cells (APC) capable of inducing strong T-cell-mediated immunity. Infusion of lymphoma-specific antigen-loaded autologous DC has been demonstrated to result in the generation of antigen-specific immunity and reduction in tumor burden in B-cell lymphoma patients. Cellular immunotherapy employing antigen-loaded DC could have a potential therapeutic impact in tumors and viral infections, including HIV infection. However, DC in HIV-infected individuals and breast cancer patients are believed to be functionally defective. Therefore, the potential of using allogeneic DC offers significant implications for DC immunotherapy in AIDS and immunocompromised cancer patients. To explore the potential of allogeneic DC therapy in vivo, we tested the ability of allogeneic DC to generate primary peptide-specific CD8+ cytotoxic T-lymphocyte (CTL) responses in vitro. Our results indicate that DC from HLA class I-matched individuals elicit primary immune responses in vitro using viral peptides as naive antigens. A primary peptide-specific immune response could also be detected even when only one HLA allele (HLA-A*0201) was matched between the allogeneic DC and T-lymphocytes. The ability to generate primary peptide-specific responses in vitro is strongly indicative of the in vivo therapeutic potential of allogeneic DC.
A rapid and highly sensitive technique (MAPPing: message amplification phenotyping) has been developed to simultaneously analyze the array of messenger RNAs made by small numbers of cells. The technique incorporates a micro-procedure for isolating RNA, reverse transcription of total cellular RNA to produce cDNA, and enzymatic amplification of cytokine-specific DNA fragments using the polymerase chain reaction. In this study, the technique has been applied to the analysis of cytokines produced by lymphoid cells ranging in number from a single cell to 10(6) cells. The technique should be applicable to virtually any tissue or cell type.