The effect of hoxb4 on self-renewal activity of memory t-cells

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Self-renewal is the division of a cell that results in the generation of a daughter cell with identical properties as the parental cell. This property is characteristic for hematopoietic stem cells (HSCs), enabling them to maintain the stem cell pool for the supply of blood cells throughout the life-time of an organism, and memory T and B cells. Memory T and B cells are responsible for long-term protection of the organism against re-infection. They develop from lymphocytes that are activated for immune response upon contact with viral or bacterial molecules. These lymphocytes undergo a massive expansion and differentiation to eliminate the pathogen. Most of them die after, but a few escapes and become memory lymphocytes that slowly turn over or self-renewal. The molecular mechanism that regulates self-renewal processes in HSCs and memory B and T cells is poorly known. Recent studies suggest that the same genes might control self-renewal in both HSCs and memory T-cells. One gene, Hoxb4, has been found to expand HSC populations, thus determining self-renewal divisions of HSCs. We hypothesize that Hoxb4 also expand the population of memory T cells. We will use a mouse model to analyse the effect of Hoxb4 on self-renewal expansion of memory T cells. If Hoxb4 determines self-renewal of memory T cells, we could not only use Hoxb4 to expand memory T cells for therapeutic use, but the more accessible memory T-cells could serve as a model to elucidate downstream targets of Hoxb4 driven self-renewal of hematopoietic stem cells and provide a source of cells to identify interacting proteins of Hoxb4 in self-renewal function as well.