Structural models for the TCR alpha/beta predict that the CDR1, CDR2, and CDR3 loops of both the alpha- and beta-chains contribute to specific interactions with the Ag/MHC complex. The CDR3 loops are constructed by joining events involving the V-(D)-J segments, and thus may vary in both sequence and length. We have developed a polymerase chain reaction assay to assess the length variation of the CDR3 loop in TCR derived from seven V beta segment families (V beta 2, V beta 3, V beta 4, V beta 9, V beta 14, V beta 16, and V beta 17). Peripheral blood T cells from 10 normal adults as well as five cord blood samples were studied. CD4+ and CD8+ T cells were analyzed separately. We observed extreme predominance of particular CDR3 lengths in half of the normal adults. These TCR were shown to be clonal by direct sequence analysis. This clonal dominance was found in the CD8+, CD45RO+ T cell population, and was observed in various V segment families. These patterns of TCR clonality were persistent over many months of observation in some individuals. In one subject, the new appearance of a predominant clone was associated with a booster vaccination for hepatitis B. These studies reveal a surprising degree of oligoclonality in the CD8+ cells of normal subjects which may be due to both environmental and genetic factors; the functional significance of persistent clonal dominance in the CD8 compartment remains to be determined.

The immune-response of macrophages is an important area of investigation since it represents the major pathway by which early-stage defense barriers are established in skin, lungs, and mucosal systems to counteract foreign objects. In this study, we have examined the size-dependent inflammatory and toxicological effects of nanostructured silver particles (nano-Ag) on macrophage immune cells.

Fas ligand (FasL) and Fas are mediators of apoptosis, which are implicated in the peripheral deletion of autoimmune cells, activation-induced T cell death, and cytotoxicity mediated by CD8+ T cells. Fas is also believed to be involved in several central nervous system diseases, but until now, the effector cells expressing FasL in the brain have not been identified. We investigated the expression levels of Fas and FasL with the stimulation of cytokines and the possible effector cells targeting Fas-bearing cells. Our data demonstrated that: 1) FasL is expressed constitutively on astrocytes taken from a fetus or an adult and that its expression increases when these cells are treated with IL-1, IL-6, or TNF-α in which the pretreatment of IFN-γ triggers astrocytes to express more FasL; 2) astrocytes induce apoptosis in MOLT-4 cells through FasL; 3) Fas is also expressed constitutively and is up-regulated by IL-1, IL-6, or TNF-α in which the pretreatment of IFN-γ triggers astrocytes to express more Fas; 4) apoptosis occurs when fetal astrocytes are treated with agonistic anti-Fas IgM Ab after culture with IFN-γ and TNF-α; and 5) TNF-related apoptosis inducing ligand is up-regulated in fetal astrocytes with stimuli of IL-1 or TNF-α. These findings suggest a possible role of astrocytes in the induction of apoptosis in central nervous system diseases.