Human peripheral blood contains two populations of dendritic cells (DC) but their developmental relationship has not been established. Freshly isolated CD11c– DC possessed a lymphoid morphology, lacked myeloid markers but expressed lymphoid markers (CD4+ CD10+) whilst the CD11c+ DC were monocytoid in appearance and expressed myeloid markers. Although both populations were allostimulatory, only the CD11c+ DC were able to take up antigen. Irrespective of the culture conditions the CD11c– cells developed into CD11c– CD13– CD33– CD4+ CD1a– CD83+/– DC. In contrast, cultured CD11c+ cells developed the phenotype CD11c+ CD13+ CD33+/– CD4– CD1a+ CD83+ CD9+. Only the CD11c+ DC expressed macrophage colony‐stimulating factor (M‐CSF) receptor and gave rise to CD14+, esterase+, phagocytic macrophages when cultured in M‐CSF. These data suggest that these two populations of DC represent distinct lineages of antigen‐presenting DC.
When cattle infected with infectious bovine rhinotracheitis virus (IBRV) were treated 3 months later with a synthetic corticosteroid, consistent recrudescence of the infection was observed. Suppression of cell-mediated immunity, as measured by lymphocyte transformation responses, could be demonstrated at the time of recrudescence. Treatment with adrenocorticotropic hormone and trigeminal neurotomy also resulted in recrudescence of IBRV, but immunosuppression was not detected in these animals. The detection of specific, antigen-induced, lymphocyte transformation responses at the time of recovery from both primary and recurrent infections suggests that cell-mediated immunity may be important in determining the duration and severity of the recurrent infection. However, immunosuppression may not be the direct mechanism of recrudescence. Lesions were not observed in untreated animals, and virus could not be detected in either tissues or secretions. However, both lesions and virus were found consistently after corticosteroid treatment.
The adhesive interactions of hemopoietic cells within the bone marrow regulate their distribution, growth, and development. Fucosylated structures, of which sialyl Lewis x has been most extensively studied, are important ligands for selectins, but little is known about their function or regulation during normal hemopoietic development. We have studied alpha 1,3-fucosyltransferase activity in CD34 positive progenitors and myeloid cells at different stages of maturation isolated form normal human bone marrow, together with mRNA levels of Fuc-TIV and Fuc-TVII. Enzyme activity measured with H type 2 acceptor was present at all stages but was markedly elevated in fractions of early myeloid cells enriched for promyelocytes, correlating with the appearance of Lewis x on these cells, and thereafter fell progressively as cells matured. Activity measured with 3'sialyllactosamine was present in CD34+ cells and at all stages of maturation. Levels were low in promyelocyte/myelocyte transitional cells and increased, relative to those measured with H type 2, during the later stages of maturation; these changes correlate directly with a maturation-related increase in sialyl Lewis x expression. Using competitive quantitative RT-PCR, mRNA levels of Fuc-TIV and Fuc-TVII were similar in CD34+ cells, early myeloid and late myeloid cells. The significance of these findings in relation to fucosyltransferase activity, the synthesis of selectin ligands and differences between normal cells and leukemic cell lines is discussed.
Advances in understanding the role of dendritic cells (DCs) as the major antigen (Ag)-presenting cell type of the immune system combined with the recent development of methods for the ex vivo expansion of human DCs have opened the possibility for the transfer of tumor Ags to DCs with a view toward tumor immunotherapy. In this study, we examined the feasibility of Ag transfer to cultured human DCs using the host range-restricted avipoxvirus, fowlpoxvirus (FWPV). FWPV was found to infect and express a lacZ marker gene in a number of mammalian cell lines of fibroblastic, epithelial, and hemopoietic lineage origins. LacZ recombinant FWPV (rFWPV) was found subsequently to infect human DCs that had been cultured ex vivo from peripheral blood monocytes. Using rFWPV containing lacZ under the control of a vaccinia virus (VV) early/late promoter (p7.5K) and a 10 plaque-forming units per cell multiplicity of infection, Ͼ80% of cells expressed the lacZ marker gene. Quantitative analysis showed that the level of expression continued to rise for 5 days postinfection, at which point the experiments were terminated. Replication-competent recombinant VV (rVV) was also shown to be capable of transferring the marker gene to primary DC cultures. However, neither rFWPV nor rVV were able to express transgenes under the control of late viral promoters, indicating that both rFWPV and rVV infections are arrested at an early stage in human DCs. Infection of CD83 ϩ DCs by rFWPV was confirmed by double-staining cytochemistry. We conclude that host range-restricted FWPV can be used efficiently to transfer Ag genes to human DCs ex vivo and may have a role in the development of tumor immunotherapy protocols.
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