Levels of Regulatory T Cells and Invariant Natural Killer Cells and Their Associations with Regulatory B Cells in Patients with Non-Hodgkin Lymphoma

Due to their immunoregulatory properties, several specialized cell subsets, including regulatory T (Treg), invariant natural killer T (iNKT) and regulatory B (Breg) cells, are involved in the pathogenesis of non-Hodgkin lymphoma (NHL). However, the interaction between various cells remains to be elucidated. The aim of the present study was to evaluate the levels of Treg, iNKT and Breg cell subsets and their interrelationships in the peripheral blood (PB) and bone marrow (BM) of patients with B-cell NHL who received rituximab-based regimens and achieved a complete remission. A total of 20 patients and 20 healthy age- and sex-matched controls were prospectively enrolled for investigation of Treg, iNKT and Breg cell subsets in PB and BM by flow cytometry and cell culture. Prior to administration of combination chemotherapy with rituximab, the patients had lower levels of Breg cells and, to a lesser degree, Treg cells, but not iNKT cells, in PB compared with controls. Compartmental differences in the levels of Treg and Breg cell subsets, but not iNKT cells, were observed between PB and BM, suggesting an increase in trafficking through the blood of these regulatory cell subsets to the marrow. Following complete remission, the levels of circulating Treg, iNKT and Breg cell subsets increased. The levels of Treg cells were not significantly associated with iNKT and Breg cell subsets, although negative correlations were observed. Taken together, these results may provide new insights into the potential role of regulatory cell subsets in patients with B-cell NHL. However, whether the observed differences between PB and BM may affect clinical outcomes requires further investigation.