Journal article
Origins of T‐cell‐mediated autoimmunity in acquired aplastic anaemia
British journal of haematology, v 206(4), pp 1035-1053
Apr 2025
PMID: 39836983
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Acquired aplastic anaemia (AA) is an autoimmune bone marrow failure disease resulting from a cytotoxic T‐cell‐mediated attack on haematopoietic stem and progenitor cells (HSPCs). Despite significant progress in understanding the T‐cell repertoire alterations in AA, identifying specific pathogenic T cells in AA patients has remained elusive, primarily due to the unknown antigenic targets of the autoimmune attack. In this review, we will synthesize findings from several decades of research to critically evaluate the current knowledge on T‐cell repertoires in AA. We will highlight new insights gained from recent in vitro studies of candidate autoreactive T cells isolated from AA patients and will discuss efforts to identify shared T‐cell clonotypes in AA. Finally, we will discuss emerging evidence on the potential T‐cell cross‐reactivity between HSPC and common viral epitopes that may contribute to the development of AA in some patients. We conclude by highlighting the areas of consensus and limitations, as well as the ongoing uncertainties, and we identify promising directions for future research in the field. Acquired aplastic anaemia (AA) is an autoimmune bone marrow failure disease caused by a cytotoxic T‐cell–mediated attack on haematopoietic stem and progenitor cells (HSPCs). Despite significant progress in understanding T‐cell repertoire alterations in AA, the identification of specific pathogenic T cells remains elusive. Multiple studies have shown altered T‐cell homeostasis in AA patients, including increased T‐cell clonality—particularly among CD8+ T cells—and a deficit in regulatory T cells. Furthermore, no singular expanded clone or shared T‐cell clonotype unique to anaemia has been identified, suggesting that autoreactive T cells are not necessarily disease‐specific. Instead, these T cells may be present in healthy individuals without causing disease unless particular conditions (e.g. defects in immune regulatory cells, an immune dysregulatory state or a precipitating event) lead to a breakdown of immune tolerance and the activation of T cells recognizing self‐antigens on HSPCs. On the left, the figure depicts early T‐cell development and the process of negative selection against self‐reactive T‐cell clones—some of which may nonetheless mature with the potential to react against self‐antigens expressed on HSPCs. On the right, the figure illustrates the circumstances required for the induction of autoimmunity in AA.
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Details
- Title
- Origins of T‐cell‐mediated autoimmunity in acquired aplastic anaemia
- Creators
- Aura Enache - Drexel UniversityShannon A. Carty - University of MichiganDaria V. Babushok (Corresponding Author) - Children's Hospital of Philadelphia
- Publication Details
- British journal of haematology, v 206(4), pp 1035-1053
- Publisher
- Wiley
- Number of pages
- 19
- Grant note
- The Colton Center for Autoimmunity at Penn
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine
- Web of Science ID
- WOS:001400919700001
- Scopus ID
- 2-s2.0-85215407192
- Other Identifier
- 991022197404004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Hematology