The extent of infection and rate of pathogen clearance are thought to determine both the magnitude of antigen-specific CD8(+) T cell expansion and the ensuing contraction to a stable number of memory cells. We show that CD8(+) T cell expansion after Listeria monocytogenes infection was primarily dependent on the initial infection dose or amount of antigen displayed, and was also influenced by the rate of pathogen clearance. However, the onset and kinetics of CD8(+) T cell contraction after L. monocytogenes and lymphocytic choriomeningitis virus infections were independent of the magnitude of expansion, dose and duration of infection or amount of antigen displayed. Thus, major features of antigen-specific CD8(+) T cell homeostasis, including the contraction phase of an immune response, may be programmed early after infection.

Pathogen-specific CD8(+) T cells expand in number after infection and then their numbers invariably contract by 90-95%, leaving a stable memory cell pool. The chief features of this response are programmed early after infection; however, the factors regulating contraction are mostly undefined. Here we show that antibiotic treatment before Listeria monocytogenes infection induced numbers of protective memory CD8(+) T cells similar to those in control infected mice, by a pathway without contraction. The absence of contraction correlated with decreased early inflammation and interferon-gamma production and an increased fraction of CD8(+) T cells expressing the interleukin 7 receptor at the peak of the response. Thus, contraction is controlled by early inflammation but is not essential for the generation of protective memory CD8(+) T cells after infection.

One-third of the world’s population is infected with Mycobacterium tuberculosis (Mtb), and three million people die of tuberculosis each year. Following its ingestion by macrophages (MPs), Mtb inhibits the maturation of its phagosome, preventing progression to a bactericidal phagolysosome. Phagocytosis of Mtb is uncoupled from the elevation in MP cytosolic Ca2+ that normally accompanies microbial ingestion, resulting in inhibition of phagosome-lysosome fusion and increased intracellular viability. This study demonstrates that the mechanism responsible for this failure of Ca2+-dependent phagosome maturation involves mycobacterial inhibition of MP sphingosine kinase. Thus, inhibition of sphingosine kinase directly contributes to survival of Mtb within human MPs and represents a novel molecular mechanism of pathogenesis.

Blubber samples from male California sea lions (Zalphophus californianus)stranded between 1993 and 2003 were analyzed for 27 polybrominated diphenyl ether (PBDE) congeners, three isomers of hexabromocyclododecane (HBCD) and 14 methoxylated polybrominated diphenyl ether (MeO-BDE) congeners. Total PBDEs ranged from 450 ng/g to 4740 ng/g wet mass and total HBCD ranged from <0.3 ng/g to 12 ng/g wet mass. The concentration of HBCD increased from 0.7 ng/g to12.0 ng/g wet mass in sea lion blubber between 1993 and 2003. However, no significant temporal trend was observed for any of the other brominated compounds over this ten year period.Only one of the 14 MeO-BDE congeners was detected in the blubber samples, 6-methoxy-2,2',4,4'-tetrabromodiphenyl ether (6-MeO-BDE 47), and concentrations ranged from <0.2 ng/g to 12 ng/g wet mass. A bromo-, chloro-heterocyclic compound, 1,1'-dimethyl-tetrabromo-dichloro-2,2'-bipyrrole (DBP-Br 4 Cl 2 ), previously reported in marine species along the Pacific coast, was also identified in the sea lion blubber. DBP-1 Br 4 Cl 2 ranged from 44 ng/g wet mass to 660 ng/g wet mass and was present at concentrations rivaling the dominant PBDE congener, BDE 47 (2,2',4,4'-tetrabromodiphenyl ether). Concentrations of DBP-Br 4 Cl 2 were positively correlated with 6-MeO-BDE 47 (r= 0.7; p<0.05). Both of these compounds have been identified in marine algae and sponges, and studies suggest they are both produced from natural sources. This study demonstrates that brominated compounds from both anthropogenic and biogenic sources can accumulate to similar levels in marine mammals. In addition, HBCD concentrations appear to be increasing in California sea lion populations, whereas PBDE concentrations, between 1993 and 2003, were highly variable.

Objective. To compare the effect of 3 wrist splints (2 prefabricated commercial splints and 1 custom made) on perceived wrist pain, hand function, and perceived upper extremity function in adults with inflammatory arthritis. Methods. Subjects (n ‫؍‬ 45, mean age 49 years, mean disease duration 8.6 years) were randomly assigned to treatment order in a 3-phase crossover trial. Splints were worn for 4 weeks, separated by 1-week washouts. Outcomes were assessed at baseline, after each splint phase and washout period, and at 6 months' followup using a pain visual analog scale (VAS), the Arthritis Hand Function Test, and McMaster-Toronto Arthritis Patient Function Preference questionnaire. Data were analyzed with multivariate analyses of variance (MANOVAs), t-tests, and chi-square tests.Results. There did not appear to be order or carryover effects. MANOVA indicated that wrist splints significantly reduced pain (P ‫؍‬ 0.007). The custom leather splint was most effective in reducing pain, from 4.1 cm to 2.8 cm on the VAS (P ‫؍‬ 0.001). All splints improved hand strength, and the commercial Rolyan splint provided significantly stronger grip than the Anatech commercial splint (P ‫؍‬ 0.04). In contrast to previous studies, splints did not compromise dexterity. There were several significant differences among splints, depending on the outcome measure. Improvements were maintained at 6 months. Conclusion. After 4 weeks' use, wrist splints reduce pain, improve strength, and do not compromise dexterity. Similar improvements were achieved with the custom leather splint and Rolyan commercial splint, which were superior to the Anatech commercial splint.