Sensory organs of the vertebrate inner ear contain two major cell types: hair cells (HCs) and supporting cells (SCs). To study the lineage relationships between these two populations, replication-defective retroviral vectors encoding marker genes were delivered to the otic vesicle of the chicken embryo. The resulting labeled clones were analyzed in the hearing organ of the chicken, called the basilar papilla (BP), after cellular differentiation. BPs were allowed to develop for 2 weeks after delivery of the retrovirus, were removed, and were processed histochemically as whole mounts to identify clones of cells. Clusters of labeled cells were evident in the sensory epithelium, the nonsensory epithelium, and in adjacent tissues. Labeled cell types included HCs, two morphologically distinct types of SCs, homogene cells, border cells, hyaline cells, ganglion cells, and connective tissue cells. Each clone was sectioned and cell-type identification was performed on sensory clones expressing retrovirally transduced ␤-galactosidase. Cell composition was determined for 41 sensory clones, most of which contained both HCs and SCs. Clones containing one HC and one SC were observed, suggesting that a common progenitor exists that can remain bipotential up to its final mitotic division. The possibility that these two cell types may also arise from a mitotic precursor during HC regeneration in the mature basilar papilla is consistent with their developmental history.

We recently established that molecular chimeras of major histocompatibility complex (MHC) class II molecules, created via retroviral transfer of allogeneic class II cDNAs into bone marrow cells (BMCs), alleviated complications associated with mixed BMC chimeras while leading to T cell tolerance to renal grafts sharing the transferred class II. Initially demonstrated for allogeneic transplants in miniature swine, this concept was extended to T-dependent antibody (Ab) responses to xenogeneic antigens (Ags) in the pig --> baboon combination. Successful down-regulation of T cell responses appeared, however, to be contingent on a tight lineage-specific expression of transferred class II molecules. The present studies were, therefore, designed to evaluate the influence of construct design and cellular environment on expression of retrovirally transferred xenogeneic class II cDNAs. Proviral genomes for pig class II SLA-DR expression, differing only at the marker neo(r) or enhanced green fluorescent protein (EGFP) gene, showed increased membrane SLA-DR density on HLA-DR(-) fibroblasts as well as HLA-DR(+), TF-1 erythroleukemia cells. More importantly, HLA-DR(+) human B cell lines, although efficiently transduced with pig DR retroviruses, exhibited unstable surface pig DR. Surface pig DR- B cells, nevertheless, stimulated autologous human T cells pre-sensitized to pig Ags, a proliferation likely occurring through presentation of class II-derived peptides. Collectively, these data suggest that surface expression of transferred class II molecules is not related to the ability of recipient cells to synthesize xenogeneic class II molecules but rather to their Ag processing capacities.

Infectious bursal disease ( IBD ) is an acute, highly contagious, economically important disease of young chickens caused by Avibirnavirus , the infectious bursal disease virus ( IBDV ). The causative virus is highly resilient in poultry environments and vaccination is the most effective measure for IBDV control. However, the susceptibility of highly attenuated IBDV vaccine strains to neutralization by maternally derived antibodies ( MDA ) and overwhelming virulence of partly attenuated strains have limited the application of conventional live IBDV vaccines in pre- and posthatch chicks. Nevertheless, preliminary data have raised questions about the validity of this prevailing dogma. India is an IBD endemic country and the disease causes sizeable economic losses in the sector. To evaluate the feasibility of application of live IBDV vaccine strain, the IBDV MB-1, to the maternally immunized day-of-hatch chicks in Indian production environment, 4 large-scale field trials have been conducted. The 4 trials have measured the relative safety, IBDV immunization parameters, and production performances of MB-1 vs. the established live and immune complex IBDV vaccines in a variety of commercial broiler systems. The overall health and production performances in all 4 trials have been better in the MB-1 groups. The results challenge the prevailing notion that live IBDV strains may be neutralized or break through maternal immunity and induce permanent damage to the young broiler chick's immune response. A delayed replication phenomenon following parenteral administration of the live IBDV vaccine strain has been observed, while the delayed replication mechanism remains to be elucidated. This study warrants further research on the molecular mechanism of live IBDV vaccine strain, MB-1, and its interaction with the chicken immune system.