Lymphocyte developmental dynamics

T cells, unlike other blood cells, finalize development in the thymus. We are trying to understand migration of progenitor cells from bone marrow to the thymus in molecular and quantitative terms. To this end, we have recently identified two receptors, CC chemokine receptors 7 and 9, which coordinate colonization of the thymus by progenitor cells. In addition, we have characterized these progenitors by defining minimal common characteristics. We demonstrated that indeed multiple different population act as physiologic thymus seeding progenitors. Recently, we employed a novel approach of multi-congenic fate mapping to quantitate the number of intrathymic niches for thymus seeding progenitors and defined feedback mechanisms that control thymus colonization. Currently, we are developing models of tissue homeostasis in thymus at high resolution. Our experiments have implications for designing pre-transplant conditioning regimens efficiently supporting thymus colonization. Ultimately our experiments are aimed at establishing a complete quantitative spatio-temporal model of early T cell development.

Key publications:

Coppin E, Sundarasetty BS, Rahmig S, Blume, Verheyden NA, Bahlmann F, Ravens S, Schubert U, Schmid J, Ludwig S, Geissler K, Guntinas-Lichius O, von Kaisenberg C, Groten T, Platz A, Naumann R, Ludwig B, Prinz I, Waskow C*, Krueger A* (2021). Enhanced differentiation of functional human T cells in NSGW41 mice with tissue-specific expression of human interleukin-7. Leukemia, 35(12):356.  * Equal contribution

Robert PA, Kunze-Schumacher H, Greiff V, Krueger A (2021). Modeling the Dynamics of T-Cell Development in the Thymus. Entropy 23(4):437.

Krueger A, Ziętara N, Łyszkiewicz M (2017). T cell development by the numbers. Trends Immunol 38:128-139.

Ziętara N, Łyszkiewicz M, Puchałka J, Witzlau K, Förster R, Pabst O, Prinz I, Krueger A (2015). Multicongenic fate mapping quantification of dynamics of thymus colonization. J Exp Med 212:1589-1601.

Łyszkiewicz M, Ziętara N, Föhse L, Puchałka J, Diestelhorst J, Witzlau J, Prinz I, Schambach A, Krueger A (2015). Limited niche availability suppresses murine intrathymic dendritic-cell development from non-committed progenitors. Blood 125:457-64.