The means by which T-regs sustain a stable pool in vivo are controversial. Using a mathematical model, we address this issue by evaluating several biological scenarios of the origins and the proliferation capacity of two subsets of T-regs: precursor CD4(+)CD25(+)CD45RO(-) and mature
CD4(+)CD25(+)CD45RO(+) cells. The lifelong dynamics of T-regs are described by a set of ordinary differential equations, driven by a stochastic process representing the major immune reactions involving these cells. The model dynamics are validated using data from human donors of different ages. Analysis of the data led to the identification of two properties of the dynamics: (1) the equilibrium in the CD4(+)CD25(+)FoxP3(+)T(regs) population is maintained over selleck kinase inhibitor both precursor and mature Tregs pools together, and (2) the ratio between precursor and mature T-regs is inverted in the early years of adulthood. Then, using the model, we identified three biologically relevant scenarios selleck products that have the above properties: (1) the unique source of mature T-regs is the antigen-driven differentiation of precursors that acquire the mature profile in the periphery and the proliferation of T-regs is essential for the development and the maintenance of the pool; there exist
other sources of mature T-regs, such as (2) a homeostatic density-dependent regulation or (3) thymus- or effector-derived T-regs and in both cases, antigen-induced proliferation is not necessary for the development of a stable pool of T-regs. This is the first time that a mathematical model built to describe the in vivo dynamics of regulatory T cells is validated using human data. The application of this model provides an invaluable tool in estimating the amount of regulatory T cells as a function of time in the blood of patients that received a solid organ transplant or are suffering from an autoimmune disease. (C) 2010 Elsevier Ltd. All rights reserved.”
“OBJECTIVE: A review of Harvey Cushing’s surgical cases at Johns Hopkins Hospital
revealed new Org 27569 information about his early work using nerve xenografts to repair peripheral nerve injuries.
METHODS: The Johns Hopkins Hospital surgical records from 1896 to 1912 were reviewed. A single case in which Cushing used a xenograft to repair a peripheral nerve defect was selected for further study.
RESULTS: In August 1902, a 23-year-old woman presented with tingling and numbness in her left foot and focal tenderness in the popliteal region. Cushing performed an exploratory operation, revealing an encapsulated tumor originating from the internal popliteal nerve. After resecting the segment of involved nerve, Cushing harvested the spinal cord from a rabbit and used it to span the 18-cm defect. At a 5-month postoperative follow-up, according to Cushing’s clinical notes, the patient had partially regained some sensation in her leg and foot.