Journal
ANNALS OF HEMATOLOGY
Volume 102, Issue 5, Pages 1247-1255Publisher
SPRINGER
DOI: 10.1007/s00277-023-05174-w
Keywords
Pure red cell aplasia; TOX; T lymphocyte; PD1; LAG3
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TOX expression is increased in PRCA patients, leading to CD8(+) T cell overactivation and decrease in regulatory T cells, which play a critical role in the immune pathogenesis of PRCA.
Thymocyte selection-associated high-mobility group box protein (TOX) is an important molecule regulating the development and exhaustion of T lymphocytes. Our aim is to investigate the role of TOX in the immune pathogenesis of pure red cell aplasia (PRCA). TOX expression of CD8(+) lymphocytes from the peripheral blood of patients with PRCA was detected by flow cytometry. Additionally, the expression of immune checkpoint molecules PD1 and LAG3 and cytotoxic molecules perforin and granzyme B of CD8(+) lymphocytes was measured. The quantity of CD4(+)CD25(+)CD127(low) T cells was analyzed. TOX expression on CD8(+) T lymphocytes in PRCA patients was significantly increased (40.73 +/- 16.03 vs. 28.38 +/- 12.20). The expression levels of PD1 and LAG3 on CD8(+) T lymphocytes in PCRA patients were significantly higher than those in the control group (34.18 +/- 13.26 vs. 21.76 +/- 9.22 and 14.17 +/- 13.74 vs. 7.24 +/- 5.44, respectively). The levels of perforin and granzyme in CD8(+) T lymphocytes of PRCA patients were 48.60 +/- 19.02 and 46.66 +/- 25.49, respectively, which were significantly higher than those of the control group (31.46 +/- 7.82 and 16.17 +/- 4.84, respectively). The number of CD4(+)CD25(+)CD127(low) Treg cells in PRCA patients was significantly decreased (4.30 +/- 1.27 vs. 1.75 +/- 1.22). In PRCA patients, CD8(+) T cells were activated and exhibited overexpression of TOX, PD1, LAG3, perforin, and granzyme B, while regulatory T cells decreased. These findings suggest that T cell abnormality plays a critical role in the pathogenesis of PRCA.
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