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Rare disorder gives modelers first glimpse at immune system development
Date:6/16/2009

DURHAM, N.C. -- Children born without thymus glands have given Duke University Medical Center researchers a rare opportunity to watch as a new immune system develops its population of infection-fighting T-cells.

Researchers led by Thomas Kepler, Ph.D., Division Chief of Computational Biology, tracked three young patients after thymus tissue transplantation to measure the growth of a T cell population with all of its diversity. Duke University pioneered thymus transplantation for children born with DiGeorge Syndrome, lacking a thymus, under the direction of Louise Markert, M.D., Ph.D.

As transplanted thymus tissue took hold in the children, the team studied signals related to specific T-cell receptors and more general resources like cytokine signals or space availability. They assessed T cell receptor diversity to determine overall T cell levels and to count T cells of certain kinds.

"What we haven't understood until now is how maintaining the diversity of T cells with different receptors works while a body also maintains appropriate T cell numbers overall," said Kepler, who is senior author of a paper published in PloS Computational Biology. "Our paper is the first to use information about changes in T cell receptor diversity to infer properties of the T cell regulatory mechanisms."

The immune system needs a variety of different T cells to fight all kinds of pathogens. "The fastest way to grow the total T cell population is to impede diversity and grow just a few kinds of T cells," Kepler said. "We set out to understand more about the regulation of this fine balance."

Kepler and lead author Stanca Ciupe, Ph.D., a postdoctoral fellow in computational immunology, created mathematical formulas to model the contribution of resources on the regulation of T cell population growth and diversity. They found that factors that are blind to T cell receptors and treat all T cells alike are a thousand times more commo
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Contact: Mary Jane Gore
mary.gore@duke.edu
919-660-1309
Duke University Medical Center
Source:Eurekalert

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