"We now have a pattern to look for when we try to boost or prevent immune responses. 'Clusters' of cells in a lymph node such as we have seen may be indicative of certain unbridled T cell responses. The ultimate hope here is that seeing patterns of T cell activation may ultimately allow similar imaging to be used for diagnostic purposes," Krummel said.
Immunologists have long sought to harness the potent immunosuppressive properties of the regulatory T cells to treat autoimmune diseases and organ transplant rejection. By pinpointing where and how regulatory T cells work in vivo in mouse models, the researchers hope to better adapt the regulatory T cells for therapeutic use in the future. For example, Tang said, one can imagine that at the early stage of an autoimmune attack, it may be very helpful to direct the therapeutic regulatory T cells to the lymph nodes so they interact with dendritic cells before the autoimmune T cells are able to, and thereby "stamp out the initial sparks" before the disease spreads to the tissue.
Krummel notes that the research dispels some assumptions about cellular movement and interaction. Many had assumed that T cells move very little inside the lymph node. The video microscopy shows that they move about one body length per minute, and that much of the movement is quite directed, for example toward the dendritic cells, rather than random activity. These directed movements are followed by prolonged interaction between autoimmune T cells and dendritic cells that lead to proliferation of autoimmune cells and eventually tissue destruction.
Co-authors on the paper and collaborators in the research along with Tang, Krummel and Bluestone are Jason Y. Adams, a medical student at UCSF; Mingying Bi, MS, staff research associate; and Brian Fife PhD, a postdoctoral fellow, all in the UCSF Diabetes Center; Aaron Tooley, a UCSF graduate student in pathology; and Richard Locksley,
Source:University of California - San Francisco