Immune Checkpoint Function of CD85j in CD8 T Cell Differentiation and Aging.

Aging is associated with an increased susceptibility to infection and a failure to control latent viruses thought to be driven, at least in part, by alterations in CD8 T cell function. The aging T cell repertoire is characterized by an accumulation of effector CD8 T cells, many of which express the negative regulatory receptor CD85j. To define the biological significance of CD85j expression on CD8 T cells and to address the question whether presence of CD85j in older individuals is beneficial or detrimental for immune function, we examined the specific attributes of CD8 T cells expressing CD85j as well as the functional role of CD85j in antigen-specific CD8 T cell responses during immune aging.

Expression of CD39 on Activated T Cells Impairs their Survival in Older Individuals.

In an immune response, CD4(+) T cells expand into effector T cells and then contract to survive as long-lived memory cells. To identify age-associated defects in memory cell formation, we profiled activated CD4(+) T cells and found an increased induction of the ATPase CD39 with age. CD39(+) CD4(+) T cells resembled effector T cells with signs of metabolic stress and high susceptibility to undergo apoptosis.

Neuromagnetic evidence of abnormal movement-related beta desynchronization in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder associated with debilitating motor, posture, and gait abnormalities. Human studies recording local field potentials within the subthalamic nucleus and scalp-based electroencephalography have shown pathological beta synchronization throughout the cortical-basal ganglia motor network in PD. Suppression of such pathological beta synchronization has been associated with improved motor function, which may explain the effectiveness of deep-brain stimulation.

Inflammation and adaptive immunity in Parkinson's disease.

The immune system is designed to protect the host from infection and injury. However, when an adaptive immune response continues unchecked in the brain, the proinflammatory innate microglial response leads to the accumulation of neurotoxins and eventual neurodegeneration. What drives such responses are misfolded and nitrated proteins.

Pathways towards an effective immunotherapy for Parkinson's disease.

Immunizations that target specific types of immune responses are used commonly to prevent microbial infections. However, a range of immune responses may prove necessary to combat the ravages of neurodegenerative diseases. The goal is to eliminate the 'root' cause of neurodegenerative disorders, misfolded aggregated proteins, while harnessing adaptive immune responses to promote neural repair.

Murine motor and behavior functional evaluations for acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication.

Acute intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces nigrostriatal neurodegeneration that reflects Parkinson's disease (PD) pathobiology. The model is commonly used for rodent studies of PD pathogenesis and diagnostics and for developmental therapeutics. However, tests of motor function in MPTP-intoxicated mice have yielded mixed results.