Studies of gamma delta T cell activation: From the intestine to the spleen and also in silicon

The roles of gamma delta T cells in the immune system have remained unclear. In the spleens and lymph nodes of adult animals, only about 5% of lymphocytes are gamma delta T cells. On the other hand, about half of the approximately 10 million lymphocytes in the murine intraepithelial lymphocyte (IEL) compartment of the small intestine are gamma delta T cells. A microarray analysis of gamma delta IELs from normal mice and from mice infected with the enteric pathogen Yersinia pseudotuberculosis was performed to analyze how these cells respond to infection and revealed that their mRNA transcripts do not show major changes following infection and that gamma delta IELs appear to be constitutively activated. To further study gamma delta T cells, RAG2-deficient BALB/c mice that were transgenic for the G8 gamma delta T cell receptor (TCR) were used. G8 gamma delta T cells can be activated through the recognition of the MHC class Ib molecules T10 and T22 of the b but not of the d haplotype. Microarray studies of G8 gamma delta IELs reveal that they are also constitutively activated---even in the apparent absence of a stimulatory TCR ligand. In addition, while the exposure of G8 gamma delta IELs to ligand-expressing splenocytes leads to their expression of CD69 and blasting, this only leads to minor changes to their transcripts. On the other hand, the coculture of splenic gamma delta T cells from these mice with stimulatory TCR ligand-expressing splenocytes leads to their activation and their expression of cell-surface molecules like CD5, CD6, CD44, CD69, Lag-3, and PD-1. Furthermore, activated splenic gamma delta T cells are found to produce interferon gamma and interleukin 4 that act synergistically to activate B cells. In fact, the presence of both of these cytokines leads to the expression of CD69 by about 80--90% of B cells and their upregulation of B7.2, MHC class II, and T10/T22. Finally, in order to study gamma delta T cell activation and immunological synapse formation, a simulation of cell-to-cell contact was designed using the JAVA programming language.