[Exhaustion of CD8T Lymphocytes Plays a Critical Role in the Pathogenesis of Secondary Hemophagocytic Lymphohistiocytosis].

Objective: To investigate the changes in function of CD8 T cell subsets, and explore its significance in pathogenesis of secondary hemophagocytic lymphohistiocytosis (sHLH).

Methods: Flow cytometry was used to detect the expressions of PD-1, TIM-3, and LAG-3, which were the markers of exhausted CD8 T cell, as well as the secretion levels of interferon γ (IFN-γ) and expression of ΔCD107a after the stimulation; the numbers of effector-memory CD8 T cells, regulatory T cells and double negative T cells were also detected.

Results: The expressions of inhibitory receptors (PD-1, TIM3 and LAG-3) on CD8 T cells of sHLH patients were 40.73±22.64, 15.97±14.45 and 0.73 (0-37.41), respectively, which were significantly higher than those of the control group (P<0.001). In contrast, the expression of ΔCD107a (4.49±2.71 vs 6.07±2.14, P=0.035) and secretion level of IFN-γ (37.30±24.46 vs 55.17±22.23, P=0.034) were significantly lower. The number of effector-memory CD8 T cells in sHLH patients was also lower as compared with that in control group (14.35±10.37 vs 22.92±11.12, P=0.016). But there was no significant difference in the number of regulatory T cell and double negative T cell. In addition, the expressions of PD-1, TIM3 and LAG-3 in active stage of sHLH were 38.09±21.87, 14.35±13.70 and 0.82 (0-13.22), respectively, which were significant higher than those in remission stage [24.27±17.23 (P=0.03), 8.64±5.60 (P=0.014) and 0.13 (0-3.69)].

Conclusion: The exhausted CD8 T lymphocytes may play a critical role in the development of sHLH.