Origins of T-cell-mediated autoimmunity in acquired aplastic anaemia

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.