ABSTRACT: This lab investigates how protein-carbohydrate interactions affect cell fate in the immune system. The specific focus is on the mechanism of galectin-1 mediated death of T lymphocytes, and the role of galectin-1 in immune development, lymphocyte homeostasis, response to pathogens, autoimmunity and tumor cell evasion of the immune response. T cell memory, the ability of T cells to respond to recall antigens rapidly and effectively, is a critical component of the adaptive immune response and the essential target of vaccine development. After naive T cells are exposed to a new antigen (or pathogen), expansion of antigen-specific T cells creates an effector population; the majority of effector T cells die once the antigen or pathogen is cleared. A small subset of T cells remains after antigen is cleared, the memory T cells. These memory cells can respond more rapidly than naive cells to recall antigen, and are also capable of homeostatic self-renewal. During the development of T cell memory, there are dramatic changes in gene transcription, protein expression and post-translational modification of proteins, compared to naive and effector T cells. Our labs have described some of these changes at the phenotypic level, and have found important distinctions in the glycotypes of naive, effector and memory T cells. However, there has not been a systematic examination of differential glycosyltransferase expression among these T cell populations. Gene expression during the development of T-cell memory: After naive T cells are exposed to a new antigen (or pathogen), expansion of antigen-specific T cells creates an effector T cell population, the majority of which dies once antigen is cleared. A small subset, the memory T cells, remains after antigen is cleared. Using the LCMV system in P14 TCR transgenic mice specific for the DbGP33-41 epitope of LCMV, RNA (triplicate samples) was isolated from FACS-sorted virus-specific CD8+ T-cell populations during a time course following viral infection. The time points are day 0, day 8 (the peak of T-cell expansion following viral infection), day 15 (during the contraction or apoptotic phase), day 22 (during the transitional phase), and day 40 or later (the stable memory phase). The RNA samples were analyzed by Glyco-gene Chip analysis.
