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Antigen presentation safeguards the integrity of the hematopoietic stem cell pool

Item Type:Article
Title:Antigen presentation safeguards the integrity of the hematopoietic stem cell pool
Creators Name:Hernández-Malmierca, P. and Vonficht, D. and Schnell, A. and Uckelmann, H.J. and Bollhagen, A. and Mahmoud, M.A.A. and Landua, S.L. and van der Salm, E. and Trautmann, C. and Raffel, S. and Grünschläger, F. and Lutz, R. and Ghosh, M. and Renders, S. and Correia, N. and Donato, E. and Dixon, K.O. and Hirche, C. and Andresen, C. and Robens, Cl. and Werner, P.S. and Boch, T. and Eisel, D. and Osen, W. and Pilz, F. and Przybylla, A. and Klein, C. and Buchholz, F. and Milsom, M.D. and Essers, M.A.G. and Eichmüller, S.B. and Hofmann, W.K. and Nowak, D. and Hübschmann, D. and Hundemer, M. and Thiede, C. and Bullinger, L. and Müller-Tidow, C. and Armstrong, S.A. and Trumpp, A. and Kuchroo, V.K. and Haas, S.
Abstract:Hematopoietic stem and progenitor cells (HSPCs) are responsible for the production of blood and immune cells. Throughout life, HSPCs acquire oncogenic aberrations that can cause hematological cancers. Although molecular programs maintaining stem cell integrity have been identified, safety mechanisms eliminating malignant HSPCs from the stem cell pool remain poorly characterized. Here, we show that HSPCs constitutively present antigens via major histocompatibility complex class II. The presentation of immunogenic antigens, as occurring during malignant transformation, triggers bidirectional interactions between HSPCs and antigen-specific CD4(+4) T cells, causing stem cell proliferation, differentiation, and specific exhaustion of aberrant HSPCs. This immunosurveillance mechanism effectively eliminates transformed HSPCs from the hematopoietic system, thereby preventing leukemia onset. Together, our data reveal a bidirectional interaction between HSPCs and CD4(+4) T cells, demonstrating that HSPCs are not only passive receivers of immunological signals but also actively engage in adaptive immune responses to safeguard the integrity of the stem cell pool.
Keywords:Hematopoietic Stem Cells, Antigen Presentation, Immunosurveillance, CD4+ T Cells, Immune Regulation, Acute Myeloid Leukemia, Leukemia
Source:Cell Stem Cell
ISSN:1934-5909
Publisher:Cell Press / Elsevier
Volume:29
Number:5
Page Range:760-775.e10
Date:5 May 2022
Official Publication:https://doi.org/10.1016/j.stem.2022.04.007
PubMed:View item in PubMed

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