The human thymus is a complex chimeric organ comprised of central (thymic epithelial space) and peripheral (perivascular space) components that functions well into adult life to produce naive T lymphocytes. Recent advances in identifying thymic emigrants and development of safe methods to study thymic function in vivo in adults have provided new opportunities to understand the role that the human thymus plays in immune reconstitution in aging, in bone marrow transplantation, and in HIV-1 infection. The emerging concept is that there are age-dependent contributions of thymic emigrants and proliferation of postthymic T cells to maintain the peripheral T cell pool and to contribute to T cell regeneration, with the thymus contributing more at younger ages and peripheral T cell expansion contributing more in older subjects. New studies have revealed a dynamic interplay between postnatal thymus output and peripheral T cell pool proliferation, which play important roles in determining the nature of immune reconstitution in congenital immunodeficiency diseases, in bone marrow transplantation, and in HIV-1 infection. In this paper, we review recent data on human postnatal thymus function that, taken together, support the notion that the human thymus is functional well into the sixth decade and plays a role throughout life to optimize human immune system function.

Control of HIV-1 replication following nonsterilizing HIV-1 vaccination could be achieved by vaccine-elicited CD8؉ T-cell-mediated antiviral activity. To date, neither the functional nor the phenotypic profiles of CD8 ؉ T cells capable of this activity are clearly understood; consequently, little is known regarding the ability of vaccine strategies to elicit them. We used multiparameter flow cytometry and viable cell sorts from phenotypically defined CD8؉ T-cell subsets in combination with a highly standardized virus inhibition assay to evaluate CD8 ؉ T-cell-mediated inhibition of viral replication. Here we show that vaccination against HIV-1 Env and Gag-Pol by DNA priming followed by recombinant adenovirus type 5 (rAd5) boosting elicited CD8 ؉ T-cell-mediated antiviral activity against several viruses with either lab-adapted or transmitted virus envelopes. As it did for chronically infected virus controllers, this activity correlated with HIV-1-specific CD107a or macrophage inflammatory protein 1␤ (MIP-1␤) expression from HIV-1-specific T cells. Moreover, for vaccinees or virus controllers, purified memory CD8؉ T cells from a wide range of differentiation stages were capable of significantly inhibiting virus replication. Our data define attributes of an antiviral CD8 ؉ T-cell response that may be optimized in the search for an efficacious HIV-1 vaccine.

showed MLV particles with a weightaverage diameter of 152 nm as compared to the 232 nm found in HN buffer. This represents a water loss of 67 percent in the MLV and an increase in particle density to 1.0472 g/cm3, as compared to the 1.0154 g/cm3 assumed for the original particles.The particle size distribution data for the SUV particles are believed to be reasonably accurate even though no correction for the osmotic effect of the sucrose-buffer mixture was used in the measurement. The osmotic activity for the much smaller SUV particles is expected to be considerably less than'that for MLV as a result of molecular constraints caused by the'minimal radius of the SUV particles.In the SFFF analytical mode, it is relatively easy to collect submilligram quantities of isolate with very high resolution. If the resolution is compromised somewhat, milligram to gram quantities can be isolated by having the instrument function as a selective filter (3), retaining large liposomes while allowing smaller ones to be eluted in the mobile phase. In conjunction with extrusion techniques (7, 9), SFFF should make possible the rapid preparation of appreciable amounts of liposomes with a polydispersity close to unity. It thus appears that SFFF is a rapid, precise, and gentle method for the analysis of. the particle size distributions of noninteracting biological colloids, as we have illustrated with liposomes. We believe that SFFF will be an equally important technique in the fractionation and size analysis of other biop4 as nucleic acids and cellul such as ribosomes, mitoc] nuclei.