T cell modulation of hematopoiesis. (LSBR 1014 Fellowshipproject)
Project leader: Dr. Martijn A. Nolte, Dept. of Hematopoiesis, Adaptive Immunity Lab, Sanquin Research, Amsterdam
Postdoc: Maria Fernanda Pascutti, PhD (Oct. 2012 – May 2016)
Ph.D. student: Sulima Geerman, MSc (Nov. 2011 – Mar. 2016)
Technician: Edith Slot (Jan. 2014 – Mar. 2015)
Bone marrow is not only the organ in which new blood cells are generated, but also an immunologically active site where immune responses against pathogens can be initiated. Recognition of a virus inside the bone marrow leads, just like in lymph nodes, to the activation and expansion of virus-specific T cells, which subsequently start the hunt for virus-infected cells. It is remarkable that blood cell formation and anti-viral defense can coincide in the bone marrow, because the production of new blood cells is highly sensitive to inflammatory processes. In particular, hematopoietic stem cells can be adversely affected by the inflammatory mediators that are produced by activated T cells. As these stem cells are the source of all blood cells, strong (and especially chronic) T cell activation can lead to the development of inflammation-induced anemia. Yet, we have demonstrated in this research project that resting memory T cells in the bone marrow actually have a positive effect on hematopoietic stem cells and blood cell formation. We found that a particular subset of memory T cells secrete a molecule that enhances the proliferation of these blood stem cells and also boosts their blood cell formation upon transplantation. In addition, we found that the bone marrow can harbor many virus-specific memory T cells. We postulate that this accumulation of memory T cells is important for the regeneration of the stem cell compartment in the bone marrow, which heavily suffers from a viral infection. This study thus uncovers a new mechanism by which the immune system is able to restore blood cell formation after a (viral) infection. On the one hand, these findings provide a better understanding of the (patho-) physiological processes in the bone marrow during (chronic) infection and inflammation. On the other hand, our new insight may contribute in the near future to enhancing the efficiency of stem cell transplantation and restoration of blood formation after such demanding treatments.