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Cells on path to becoming mature T-cells more flexible than commonly thought
Date:4/9/2008

thymic progenitors, the ETPs, should be able to make T cells, but unable to make myeloid cells, explains senior author Avinash Bhandoola, PhD, Associate Professor of Pathology and Laboratory Medicine. Jeremiah instead found that progenitor cells that make it to the thymus have not yet committed to either the myeloid or T-cell pathway.

In order to determine the potential of ETPs, the team first had to separate ETPs from all the other cells in a mouse thymus. This was accomplished by sorting the cells based on surface tags that are characteristic of the ETP cell type.

Next, single ETP cells were painstakingly placed into culture so that each container received only one cell. We really wanted to examine single cells, says Bell. Otherwise, even if you do see T cells and myeloid cells, you cant be certain that they all came from the same progenitor cell. After growing and dividing for several days, the cells from each container were examined, again by surface tags, to see whether T cells or myeloid cells were present.

To the surprise of Bell and Bhandoola, most of the cultures begun with single cells had become a mixture of T cells and myeloid cells. This means that the majority of early thymic progenitor cells do not commit to becoming T cells by the time they get to the thymus gland. ETP cells retained the ability to become either T cells or myeloid cells.

Since ETPs showed the potential to give rise to myeloid cell types, the team also asked whether some of the myeloid cells in the thymus normally arise from ETPs. The process of T-cell development in the thymus requires progenitor cells to rearrange pieces of DNA. This process of DNA rearrangement is required to build the antigen receptor used by T cells, and permanently marks ETPs. Bell and Bhandoola found that permanent marks of past DNA rearrangements were present in myeloid cells within the thymus, but not in myeloid cells at other sites. This showed that ETPs give rise to
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

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