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| Item Type: | Article |
|---|---|
| Title: | Antigen presentation safeguards the integrity of the hematopoietic stem cell pool |
| Creators Name: | Hernández-Malmierca, P., Vonficht, D., Schnell, A., Uckelmann, H.J., Bollhagen, A., Mahmoud, M.A.A., Landua, S.L., van der Salm, E., Trautmann, C., Raffel, S., Grünschläger, F., Lutz, R., Ghosh, M., Renders, S., Correia, N., Donato, E., Dixon, K.O., Hirche, C., Andresen, C., Robens, Cl., Werner, P.S., Boch, T., Eisel, D., Osen, W., Pilz, F., Przybylla, A., Klein, C., Buchholz, F., Milsom, M.D., Essers, M.A.G., Eichmüller, S.B., Hofmann, W.K., Nowak, D., Hübschmann, D., Hundemer, M., Thiede, C., Bullinger, L., Müller-Tidow, C., Armstrong, S.A., Trumpp, A., 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 |
| Date: | 5 May 2022 |
| Additional Information: | Copyright © 2022 Elsevier Inc. This manuscript version is made available under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/bync-nd/4.0/ or send a letter to Creative Commons, PO Box 1866, Mountain View, CA 94042, USA. |
| Official Publication: | https://doi.org/10.1016/j.stem.2022.04.007 |
| PubMed: | View item in PubMed |
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