The role of HOX 4 paralog genes in maintenance and expansion of T memory cells

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Our immune cells patrol the body to detect and respond to external invaders, such as bacteria's and viruses. Once they have cleared the attack, a few immune cells will be kept for years, enabling us to act more efficiently in second attack of the same intruder. We refer to these cells as immunological memory. There are two classes of memory cells, those of the B-cell type (predominantly involved in bacterial infections) and of the T-cell type (predominantly involved in viral infections). The number of memory cells is very low, and to prevent their loss, due to maturation into effector immune cells upon repeated encounter with the intruder, these cells divide occasionally into two daughter cells of which at least one is exactly the same as the original cell. Blood stem cells, which are even rarer, undergo as well this type of self-renewal divisions to maintain their numbers, enabling to provide a life-time blood supply. The current thought is that molecules determining the self-renewal divisions are the same in both cell types. We are interested in understanding how to expand the T memory cell pool. The protein Hoxb4 is known to increase the blood stem cell numbers, and thus we hypothesized that this protein can expand memory cells as well. Our first results show indeed a better expansion of a T memory cell subset in the presence of Hoxb4 than control. Using mice we want to test whether these expanded memory cells can produce an immune response. Furthermore, other memory cell subsets will be tested for expansion with Hoxb4 in cell culture and in a mouse. Finally, we will investigate the relation between Hox genes and other molecules (Wnt) that have recently been shown to be important in memory T cells.