Faculty Bibliography

Nonreplicating vectors are being considered in HIV-1 vaccine design. However, nonreplicating viruses are typically weak immunogens, leading to efforts to target the vaccine to mature dendritic cells (DCs). We have studied a single-cycle form of HIV-1, prepared by pseudotyping envelope-defective HIV-1 plasmids with the envelope from vesicular stomatitis virus (VSV) G protein (VSV-G), to which most humans lack preexisting immunity. The nonreplicating, VSV/HIV-1 efficiently infected the immature stage of DC development, in this case represented by monocytes cultured with GM-CSF and IL-4. A majority of the cells reverse transcribed the HIV-1 RNA, and a minority expressed gag protein. The infected populations were further matured with CD40 ligand, leading to strong stimulation of autologous T cells from HIV-1-infected individuals, but not controls. Enriched CD8(+) T cells from 12/12 donors released IFN-gamma (50-300 enzyme-linked immunospots/200,000 T cells) and proliferated. Macrophages were much less efficient in expanding HIV-1-responsive T cells, and bulk mononuclear cells responded weakly to VSV/HIV-1. CD4(+) T cells from at least half of the donors showed strong responses to VSV/HIV-1-infected DCs. Presentation to CD8(+) T cells, but not to CD4(+), was primarily through an endogenous pathway, because the responses were markedly reduced if envelope-defective virus particles or reverse transcriptase inhibitors were added. Therefore, nonreplicating vaccines can be targeted to immature DCs, which upon further maturation induce combined and robust CD4(+) and CD8(+) immunity.

PURPOSE: To determine the best plane and position of the elbow for optimal visualization of normal and abnormal collateral ligaments with conventional magnetic resonance (MR) imaging and MR arthrography, to determine the normal appearance of the collateral ligaments at MR arthrography and to assess use of MR arthrography in evaluation of collateral ligamentous lesions. MATERIALS AND METHODS: Nine cadaveric elbow specimens were imaged with and without intraarticular administration of gadolinium-containing solution in several planes that were identified as potentially useful in a pilot study in two specimens. MR imaging findings were compared with anatomic findings. RESULTS: Normal and abnormal ligaments were best depicted in a 20 degrees posterior oblique coronal plane in relation to the humeral shaft with the elbows extended and a coronal plane aligned with the humeral shaft with the elbows slightly flexed (20 degrees-30 degrees of flexion). Gadolinium enhancement improved the delineation of normal and abnormal ligaments on T1-weighted images in each case. CONCLUSION: The posterior oblique coronal plane with the elbows extended or the coronal plane aligned with the humeral shaft with the elbows slightly flexed allows accurate assessment of the collateral ligaments. Gadolinium-enhanced MR arthrography of the elbow seems to be a promising technique.