Abstract

We are interested in the question of lineage specification and commitment in the lymphoid system. We are focusing in particular on the aspect how adhesion molecules compartmentalise haematopoietic and lymphoid progenitors and how these alterations affect the developmental potential and mircoanatomical localisation of progenitors and lymphocytes.

Remarkably, beta1 integrin is not absolutely required for the migration of adult lymphoid progenitors but seems to exert some functions in the induction and regulation of an immune response. In conjunction with our studies on the alpha4 integrin we hope to define the different requirements for these adhesion molecules in lymphopoiesis and during an immune response by various genetical approaches including the generation of humanised mouse models for integrin expression.

While the relationship between haematopoietic stem cells and progenitor populations has been extensively investigated under steady state conditions, the dynamic response of the haematopoietic compartment to acute infection is largely unknown. To gain further insights into this process we analysed the alterations of haematopoietic differentiation and migration of progenitors in mice with acute of malaria.

In addition to a profoundly impaired generation of myeloid and erythroid cells we observed the cessation of lymphopoiesis combined with the transient emergence of a novel subsets of early progenitors. The generation of these infection-induced progenitors was critically dependent on IFN -gamma signalling and might be part of an early host defence mechanism for the control of pathogens. We are currently extending these studies focusing on the role of integrins for the dynamic changes of haematopoiesis in infection.

In summary, we believe that a better understanding for the compartmentalisation and the physiological or pathological mobilisation of haematopoietic cells can directly lead to more informed therapies and drug design.