3071 – HEALTHY AND MALIGNANT HEMATOPOIETIC STEM CELLS ACT AS IMMUNOREGULATORY ANTIGEN PRESENTING CELLS

• Published in: Experimental hematology Vol. 100; p. S76
• Main Authors: Hernández-Malmierca, Pablo, Vonficht, Dominik, Schnell, Alexandra, Kuchroo, Vijay, Trumpp, Andreas, Haas, Simon
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.08.2021
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2021.12.289

Hematopoietic stem cells (HSCs) continuously generate blood and immune cells, including T cells and antigen-presenting cells (APCs). Antigen presentation by APCs to CD4+ helper T cells constitutes the central process in the orchestration of adaptive immune responses. While T cells play a vital role in regulating stem cell biology, stem cells are not considered to actively modulate the adaptive immune system. Here, we show that healthy and malignant HSCs act as APCs capable of inducing antigen-specific T cell responses in mouse and human. This interaction efficiently activates T cells and polarizes them towards an immunoregulatory state. Moreover, transient antigen presentation triggers a rapid cell cycle induction and differentiation of HSCs upon interaction with antigen-specific T cells, whereas chronic antigen presentation resulted in irreversible stem cell exhaustion. In malignant hematopoiesis, antigen presentation was associated with a stem-like state and poor clinical outcome. Our data reveal a bidirectional interaction between stem cells and the adaptive immune system, demonstrating that normal and malignant HSCs are not only passive receivers of immunological signals, but active modulators of their microenvironment.