The following is a summary of “The role of CD8+ T-cell clones in immune thrombocytopenia,” published in the May 2023 issue of Hematology by Malik et al.
Immune thrombocytopenia (ITP) is traditionally regarded as an antibody-mediated disease. For a study, researchers aimed to know the role of CD8+ T-cell clones on ITP. They used a multidimensional methodology to investigate the involvement of cytotoxic CD8+ T cells in ITP.
Study group utilized immunophenotyping, T-cell receptor gene sequencing, single-cell RNA sequencing, and functional assays; they compared ITP patients with age-matched controls to gain insights into their role.
Their study revealed that adults diagnosed with chronic ITP exhibit higher levels of polyfunctional CD8+ T cells with characteristics of terminally differentiated effector memory cells (CD45RA+CD62L–). These cells expressed intracellular interferon-gamma, tumor necrosis factor α, and granzyme B and were classified as terminally differentiated effector memory (TEMRA) cells.
Investigators correlated the expansion of TEMRA cells with a decrease in platelet count in ITP patients, and there was no physiological exhaustion indication in these cells. Through deep sequencing of the TCR, they identified expanded T-cell clones in ITP patients. The persistence of T-cell clones over an extended period, their increased presence in patients with refractory disease, and their expansion during periods of low platelet count were observed. Combining single-cell RNA and TCR sequencing confirmed that the expanded clones corresponded to TEMRA cells.
Through in vitro model systems, they demonstrated CD8+ T cells derived from patients with ITP exhibit platelet aggregation, interferon-gamma release, and induce platelet activation and apoptosis by releasing cytotoxic granules through TCR-mediated mechanisms.
Study identified clonally expanded CD8+ T cells leading to platelet activation and apoptosis, suggesting an antibody-independent mechanism of platelet destruction in ITP.