Analysis of T-cell Function in Langerhans Cell Histiocytosis
Kenneth L. McClain MD, PhD (PI) and Carl E. Allen MD, PhD
Texas Children’s Hospital, Baylor College of Medicine – Houston, Texas USA
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Langerhans Cell Histiocytosis is a potentially fatal disease characterized by uncontrolled proliferation of a type of cell called a Langerhans Cell. Typically, Langerhans cells are located in the skin. The job of this cell is to recognize signals from the environment and to activate the immune system to respond to “danger” signals. When the Langerhans cell is activated it migrates to lymph nodes where it communicates with T-cells. The T-cells then become activated and create an inflammatory response that fights cells with “foreign” material such as viral proteins. In LCH, the pathologic Langerhans cells can be found in skin and lymph nodes, but also in virtually any other organ system. The LCH lesions are a mix of Langerhans cells, T-cells, and other cells of the immune system. In the LCH lesions, proteins that induce inflammation are found at high levels. It is not clear which cells, the Langerhans cells, the T-cells, or other cells, are producing these pro-inflammatory signals or why. In this study, we hypothesize that the T-cells are, at least in part, responsible for the uncontrolled inflammation that leads to proliferation of LCH lesions and to morbidity and mortality in patients with LCH. We propose to study this hypothesis first by characterizing the types of T-cells within the LCH lesions. We then propose to characterize the status major pro- and anti-inflammatory pathways in T-cells. Finally, we propose to compare the sets of genes expressed by T-cells within the LCH lesions in patients with varying levels of disease using microarray technology. With this technology we can evaluate the level of expression of over 30,000 genes in each group of T-cells we study. Our expectation is that this research will lead to improved understanding of the cause of LCH, and may also point to future studies that will allow us to individualize treatment for patients based on T-cell activity.