Scid.adh, A Thymic Cell Line That Mimics T-Cell Development In Vitro
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T-cell development proceeds through discrete stages that can be defined by the expression of cell surface markers such as CD4 and CD8 and the configuration of the T-cell receptor (TCR) gene loci. There is strong evidence that the early developmental steps depend on the pre-TCR. The most immature T cells (thymocytes) identified in the adult thymus are present in small numbers and express low levels of the cell surface receptor CD4. During the initial step of maturation, these CD4low precursors lose their expression of CD4 and become double negative (CD4- CD8-). These cells can progress to the CD4+CD8+ (double positive, DP) stage via intermediates that express either CD8 or CD4 (and are called immature single positives) in the absence of mature T-cell receptor complex. A small percentage of double positive cells mature further into CD4+CD8- or CD4-CD8+ cells that correspond to the endproducts of the intrathymic T-cell differentiation pathway and gradually exit the thymus to reach peripheral lymphoid organs.
Scid.adh, a cell line isolated from a spontaneous T-cell lymphoma that arose in a SCID (Severe combined immunodeficiency) mouse, was found to be capable of undergoing specific changes in gene expression in vitro in response to signals that mimic those of the pre-T cell receptor complex. These changes in gene expression mirror those observed during the pre-TCR induced maturation of CD4-CD8- double negative thymocytes to the CD4+CD8+ double positive stage.
Investigators at the Fox Chase Cancer Center have developed a T-cell lymphoma cell line able to undergo specific changes in gene expression following treatment with inducers of differentiation.
This is the only cell line characterized to date that can be induced to mimic aspects of the double negative to double positive transition in vitro. This is advantageous in that such a system will allow for both qualitative and quantitative analysis of the biochemical events that occur during this developmental step and are crucial for its regulation. In addition, through the use of specific signaling subunit chimeras, a determination of whether the pre-TCR signals can be initiated from within the cell by inducing aggregation of signaling chimeras at very specific intracellular sites can be made.
In the research laboratory, scid.adh is a useful tool for studying the complex pathway of immune cell differentiation.
Clinically, it is known that deregulation of thymocyte maturation at the double negative stage can result in lymphoma formation. Generation of a more detailed understanding of the biochemical processes involved in controlling T cell maturation from the double negative to double positive stage using this unique system may provide insights into how to prevent lymphoma formation at this particular step in T cell development.
This valuable research tool is available for licensing on an exclusive or non-exclusive basis. In addition, we are seeking research support for further characterization of the mechanisms of T cell differentiation.
No patent applications have been filed. (November 20, 2003)