Abstract
BackgroundAccumulating evidence have indicated that regulatory T cells (Tregs) play an essential role in T cell-mediated immune response and development of multiple myeloma (MM). CD4+FoxP3+ T cells are composed of three phenotypically and functionally distinct subpopulations: CD45RA+FoxP3lo resting Tregs (rTregs), CD45RA−FoxP3hi activated Tregs (aTregs) and CD45RA−FoxP3lo non-suppressive T cells (non-Tregs). We aimed to clarify the frequency and function of these three subpopulations in newly diagnosed multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS) patients. In addition, CD28−CD4+FoxP3+ Treg-like cell is a senescent regulatory T cell subset with partial suppressive function, which could be impaired during myelomagenesis.Methodswe examined 20 patients with MGUS, 26 patients with newly diagnosed MM and 18 healthy volunteers. Flow cytometric analysis in peripheral blood and bone marrow was performed for frequency study. The immunosuppressive function of Treg subsets was assessed by their ability to suppress the proliferation of responder cells in co-culture. Concentration of cytokine from the culture supernatants of proliferation assay was measured using ELISA.ResultsThe proportion of activated Tregs in CD4+ T cells was significantly higher in MGUS and MM patients than healthy controls (P = 0.01, P < 0.001) in both PB and BM; while the proportion of rTregs in MGUS, MM patients was significantly lower than that of controls (P = 0.02, P < 0.01) only in BM. There was no significant difference in frequencies of non-Tregs from MGUS to MM patients with normal controls (P = 0.14, P = 0.88). Significant increase in PB and BM Treg-like cells was observed in MGUS and MM cohort compared with healthy controls (P < 0.01, P < 0.01). Treg-like cells in MM patients were significantly higher than those in MGUS patients (P < 0.01). The inhibition rate of aTreg in bone marrow of MM patients was significantly higher than that of rTreg (P < 0.01), while the inhibition rate of non-Treg was significantly lower than that of rTreg cells (P < 0.01). Functional assays revealed the suppressive and secretory abilities of three Treg subsets were intact in MM patients.ConclusionsIn summary, aTregs and aging Treg-like cells were quantitatively altered in MGUS and MM patients, which might be associated with disease progression and prognosis.
Highlights
Accumulating evidence have indicated that regulatory T cells (Tregs) play an essential role in T cellmediated immune response and development of multiple myeloma (MM). CD4+FoxP3+ T cells are composed of three phenotypically and functionally distinct subpopulations: CD45RA+FoxP3lo resting Tregs, CD45RA−FoxP3hi activated Tregs and CD45RA−FoxP3lo non-suppressive T cells
Frequency of activated Treg (aTreg), resting Treg (rTreg) and non‐Tregs among C D4+ T cells in Peripheral Blood Quantification analysis showed that peripheral blood (PB) aTregs among CD4+ T cells were notably elevated in monoclonal gammopathy of undetermined significance (MGUS) (5.70 ± 1.50%, n = 10, P < 0.01) and MM patients (6.52% ± 1.37%, n = 16, P < 0.0001) compared with healthy adults (4.13% ± 0.84%, n = 10), while there was no difference between MGUS and MM group (P = 0.16) (Fig. 1a)
The frequency of rTregs among CD4+ T cells did not show any significance in MGUS patients (6.16% ± 1.34%, P = 0.72) and MM patients (5.69% ± 0.98%, P = 0.074) against healthy controls (6.35% ± 0.94%) (Fig. 1b)
Summary
Accumulating evidence have indicated that regulatory T cells (Tregs) play an essential role in T cellmediated immune response and development of multiple myeloma (MM). CD4+FoxP3+ T cells are composed of three phenotypically and functionally distinct subpopulations: CD45RA+FoxP3lo resting Tregs (rTregs), CD45RA−FoxP3hi activated Tregs (aTregs) and CD45RA−FoxP3lo non-suppressive T cells (non-Tregs). Accumulating evidence have indicated that regulatory T cells (Tregs) play an essential role in T cellmediated immune response and development of multiple myeloma (MM). CD4+FoxP3+ T cells are composed of three phenotypically and functionally distinct subpopulations: CD45RA+FoxP3lo resting Tregs (rTregs), CD45RA−FoxP3hi activated Tregs (aTregs) and CD45RA−FoxP3lo non-suppressive T cells (non-Tregs). We aimed to clarify the frequency and function of these three subpopulations in newly diagnosed multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS) patients. CD28−CD4+FoxP3+ Treg-like cell is a senescent regulatory T cell subset with partial suppressive function, which could be impaired during myelomagenesis. The three distinct subpopulations are as follows: (1) CD45RA+FoxP3lo resting Treg cells (rTregs) (2) CD45RA−FoxP3hi activated Treg cells (aTregs), both of which are suppressive in vitro; (3) non-suppressive CD45RA−FoxP3lo T cells (non-Tregs) which can secret immunoregulatory cytokines, such as IL-10, TGF-β and so on
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
