SummaryTo determine whether T cells, like B cells, can become clonally expanded in normal individuals as a function of age, we compared the T cell VB repertoire of cord blood to that of peripheral blood from normal donors over 65 yr of age. T cells from elderly subjects contained expanded subsets (greater than the mean + three standard deviations) ofT cell receptor (TCR) VB populations. These expanded subsets were observed primarily among CDS, but not CD4 cells, represented up to 37.5% of all CD8 cells, and were present in most elderly subjects. An expanded V~5.2/3 CD8 subset and a VB6.7a CD8 subset from separate donors were analyzed by reverse transcriptase-polymerase chain reaction, cloning and sequencing of the TCR ~ chain VDJ junction. In both cases the expanded subsets were mono-or oligoclonal while control CD4 populations were polyclonal. Using two-color flow cytometry it was possible to identify the expanded Vf36.7a subset as CD8 + CD28-CDllb + cells. In three of five random old subjects similar expansions of V~ subsets were found specifically in the CD8 + CD28-subpopulation, an interesting subset of cytotoxic T lymphocytes, known to lack proliferative responses to TCR stimuli. It is common practice to use the demonstration of donality as a diagnostic indicator for T cell lymphoma/leukemia. In view of the high frequency of expanded T clones of T cells in normal elderly subjects the diagnostic usefulness of this test should be reexamined.
The staphylococcal toxins are responsible for a number of diseases in man and other animals. Many of them have also long been known to be powerful T cell stimulants. They do not, however, stimulate all T cells. On the contrary, each toxin reacts with human T cells bearing particular V beta sequences as part of their receptors for major histocompatibility complex protein-associated antigen. The specificity of these toxins for V beta s puts them in the recently described class of superantigens and may account for the differential sensitivity of different individuals to the toxic effects of these proteins.
CD8 T cells contain a distinct subset of CD8+ CD28- cells. These cells are not present at birth and their frequency increases with age. They frequently contain expanded clones using various TCRalphabeta receptors and these clones can represent >50% of all CD8 cells, specially in old subjects or patients with chronic viral infections such as HIV-1. Herein, it is shown that a large fraction of CD8+ CD28- cells expresses intracellular perforin by three-color flow cytometry, in particular when this subset is expanded. Together with their known ability to exert potent re-directed cytotoxicity, this indicates that CD8+ CD28- T cells comprise cytotoxic effector cells. With BrdU labeling, we show that CD8+ CD28- cells derive from CD8+ CD28+ precursors in vitro. In addition, sorted CD8+ CD28+ cells gave rise to a population of CD8+ CD28- cells after allo-stimulation. Moreover, ex vivo CD8+ CD28+ cells contain the majority of CD8 blasts, supporting the notion that they contain the proliferative precursors of CD8+ CD28- cells. CD95 (Fas) expression was lower in CD8+ CD28- cells, and this subset was less prone to spontaneous apoptosis in ex vivo samples and more resistant to activation-induced cell death induced by a superantigen in vitro. Thus, the persistence of expanded clones in vivo in the CD8+ CD28- subset may be explained by antigen-driven differentiation from CD8+ CD28+ memory precursors, with relative resistance to apoptosis as the clones become perforin(+) effector cells.
SummaryHerpesviral DNA fragments isolated from AIDS-associated Kaposi's sarcoma (KS) tissue (KSHV-DNA) share homology with two lymphotropic oncogenic ~-herpesviruses, EpsteinBarr virus and Herpesvirus saimiri, and are present in the lesions of more than 95% of HIV and non-HIV-associated forms of KS, AIDS-related body cavity-based lymphomas, and AiDS-related multicentric Castleman's disease. Here we show that BC-1, a KSHV-DNA-positive, body cavity-based lymphoma cell line, produces infective herpesviral particles carrying a linear 270-kb genome that specifically transmits KSHV-DNA to CD19 + B cells. Transmission of KSHV-DNA is dependent upon a biologically active, replicating virus, since it is blocked by UV irradiation and foscarnet, an inhibitor of viral DNA-polymerase. This study represents the first isolation and transmission of the human herpesvirus-8/KS-associated herpesvirus.
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