The changes of follicular helper T cells and their associated molecules in patients with malignant lymphoid diseases and their significances

Abstract

Objective To investigate the changes of follicular helper T cells (Tfh cells) and Tfh cells associated molecules in the peripheral blood (PB) of patients with malignant lymphoid diseases (MLD) dynamically, and explore their roles on pathogenesis of the diseases. Methods Fifty-five patients with MLD were enrolled in this study,including 9 patients with acute lymphocyte leukemia (ALL), 30 patients with non-Hodgkin lymophoma (NHL) and 16 patients with multiple myeloma (MM), and 10 healthy controls (NC) of similar age were also enrolled. The percentage of CD4+ CXCR5+ cells (Tfh cells) and expression of ICOS+, PD1+ among the T cells were detected by flow cytometry (FCM), while the levels of interleukin 21 (IL-21) in plasma were detected by ELISA tests. Results The percentage of Tfh cells and expression of ICOS and/or PD-1 in PB of all untreated patients were significantly higher than those of NC (all P 0.05), and apparently lower than those who achieved PR (P 0.05), and much higher than NC (P<0.01). The concentration of IL-21 in patients were much higher than that in NC [(326.56±32.44) pg/ml] (P<0.01), and MM group<ALL group<NHL group [(445.08±36.14) pg/ml vs (474.55±33.41) pg/ml vs (498.64±68.11) pg/ml]. Multiple liner regression analysis showed that there was positive correlation between the number of Tfh cells and lactate dehydrogenase, international prognostic index (IPI) score, Ann Arbor staging system, ISS staging system, β2 microglobulin and lymphocytes percentage in bone marrow (all P<0.05). Conclusions The hyper-activation of Tfh cells might be associated with the immunopathogenesis of MLD caused by excessive expression of ICOS, PD-1 and IL-21. Testing the Tfh cells dynamically could be used to estimate the state and the remedial effect. Tfh cells and their related molecules could be potential therapeutic targets for MLD. Key words: Follicular helper T cells; CXCR5; Inducible costimulator; Programmed death 1; Interleukin 21