Nanoengineering of Immune Cell Function
- PDF / 257,809 Bytes
- 10 Pages / 612 x 792 pts (letter) Page_size
- 10 Downloads / 194 Views
1209-YY03-01
Nanoengineering of Immune Cell Function Keyue Shen1, Michael C. Milone2, Michael L. Dustin3, and Lance C. Kam1 Department of Biomedical Engineering, Columbia University, New York, NY 10027, U.S.A 2 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, U.S.A 3 Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, U.S.A. 1
ABSTRACT T lymphocytes are a key regulatory component of the adaptive immune system. Understanding how the micro- and nano-scale details of the extracellular environment influence T cell activation may have wide impact on the use of T cells for therapeutic purposes. In this article, we examine how the micro- and nano-scale presentation of ligands to cell surface receptors, including microscale organization and nanoscale mobility, influences the activation of T cells. We extend these studies to include the role of cell-generated forces, and the rigidity of the microenvironment, on T cell activation. These approaches enable delivery of defined signals to T cells, a step toward understanding the cell-cell communication in the immune system, and developing micro/nano- and material- engineered systems for tailoring immune responses for adoptive T cell therapies. INTRODUCTION The immune system protects against pathogens and other agents. The adaptive immune system, a recently evolved part of the vertebrate immune system, forms a strong line of defense against biological challenges through its ability to recognize new antigens, develop an appropriate response, and rapidly recall this action on subsequent re-exposure. T lymphocytes are a key regulatory component of this system, coordinating the activity of other cells and directly carrying out specific immune functions. Given these roles, T cell manipulation has been proposed as a therapeutic treatment for many diseases, most notably cancer [1-5]. A key step in many of these treatments, collectively referred to as adoptive immunotherapy, is the ex vivo stimulation and expansion of T cells, with subsequent re-introduction of these cells into the patient. This process is most often carried out by presenting T cells with ligands to specific receptors present on the T cell surface. The T Cell Receptor (TCR) complex which provides the primary antigenic signal conferring specificity and the CD28, and LFA-1 receptors which provide costimulatory and adhesive signals have been the most intensively used. Additional coreceptors assist TCR signaling in responding to different types of major histocompatibility complex (MHC) antigen presenting molecules. CD4 assists with recognition of extracellular peptides on MHC class II and CD8 assists with intracellular peptides presented on MHC class I. Mature T cells express CD4 or CD8 and both types of cells are valued adoptive immunotherapy. In vivo, these ligands are presented to T cells on the surface of specialized Antigen Presenting Cells (APCs), and this association with the plasma membrane is
Data Loading...
