What makes a T cell become a memory T cell?

          CD4+ T cells, also known as helper T cells (Th cells), support B and T cell immune responses (more on helper T cells).  Once activated, Th cells differentiate into different effectors, depending on chemical factors in the local environment, called cytokines.  One of these effectors is Th1, mainly involved in an antiviral response or response combating intracellular pathogens.  After the antigen has been cleared from the system, most of the Th1 cells are eliminated by immune system controls, however, a small number of the Th1 cells survive and differentiate into memory T cells.  Although the process in which Th cells differentiate into Th1 cells has been extensively studied, very little is known about the differentiation of Th1 cells into memory cells!  Knowing the steps involved in memory cell differentiation is important, because not only do they indicate the factors that effect T cell fate, but this knowledge could be used to design better vaccines that are aimed at increasing memory T cell formation!  T cell receptors (TCRs) (more on T cells and TCRs) create signals during activation that impact the differentiation and expansion of the T cell, therefore, there is a possibility that TCR signaling determines the end fate of T cells as well: whether they become long-lived memory T cells or end-stage effectors to be eliminated after the pathogen has been cleared.

            In a recent study, Kim et al investigated the impact of TCR signals on the end fate of Th1 cells.   They determined which TCR-binding characteristics correspond to memory differentiation.  To do this, they cloned TCR sequences obtained in a deep sequencing process, and then they transfected 293 T cells with TCR retroviral expression vectors so they could express these TCRs.  Next, the T cells were infected with GP 66-77 tetramer (an antigen glycoprotein), and the tetramer off rates (the rate at which TCR and pMHC dissociate) and avidity (number of TCR-pMHC interactions occurring) for TCRs were measured.  Some TCRs had high avidity with quick off rates, and some had low avidity with extremely slow off rates.  When compared to TCR survival 8-42 days after infection, the only significant predictor of memory T cell potential was the tetramer off rate.

Learning Through Your Gut

What is all the hype about probiotic yogurt these days and why would a person want to have, let alone add, bacteria into their body? The fact is that not all bacteria are bad; some can even be beneficial to our health. The role of bacteria found in the gut include helping with the digestion of food, providing vitamin K, helping protect the colon from the invasion of harmful bacteria, and helping to educate the immune system to differentiate between harmless and harmful bacteria.¹ However, it is still not well understood exactly why the body fails to trigger an immune response against these bacteria.

Our bodies fight invasion through the lymphocytes. These white blood cells are varied and one type, the T cell, produces a response against invasion by activating other cells called regulatory T cells. Lathrop and his associates set out to determine how these cells are involved in regulating immune responses in the colon.