Objective To investigate the possible factors for differentiation affecting of neonatal regulatory T cells(Treg). Methods Umbilical cord blood was collected from 200 newborns. Treg number was detected by DNA demethylation in the Foxp3 of Treg - cell - specific demethylatedregion(TSDR)based on high resolution melting anal-ysis(HRMA),concentrations of 7,8 - dihydroxy - 9,10 - epoxy - benzo(a)pyrene(BPDE - DNA)adducts and interleukin - 4( IL - 4)in the supernatants of cord blood by enzyme - linked immunosorbent assay( ELISA),and follow - up questionnaires were carried out till 1. 0 - 1. 5 years,for recurrent wheezing or stubborn eczema in infants and related information on parental history of atopic diseases. Results (1)In wheezing group[(0. 48 ± 0. 05)% ]and ec-zema group[(0. 76 ± 0. 05)% ],the number of Tregs was significantly lower compared with that of the asymptomatic group[(1. 14 ± 0. 08)% ](t = 2. 62,2. 83,all P ﹤ 0. 05);the number of Treg in parental history of atopic group was significantly lower than that of the non - atopic group(P ﹤ 0. 05);but the Treg numbers in the non - atopic group was still lower than that of the asymptomatic group(P ﹤ 0. 05).(2)The concentrations of BPDE - DNA adducts in the wheezing group[(236. 30 ± 6. 59)ng/ L]and the eczema group[(173. 40 ± 7. 38)ng/ L]were higher than those of the asymptomatic group[(111. 01 ± 3. 36)ng/ L](t = 10. 35,6. 53,all P ﹤ 0. 05),while BPDE - DNA adduct concen-trations in the atopic group with parental history of wheezing or eczema in infants were lower than those of the non -atopic group(P ﹤ 0. 05).(3)The concentrations of IL - 4 in the wheezing or eczema group in the supernatants of cord blood was higher than the asymptomatic group(P ﹤ 0. 05). Conclusions Neonatal genetic factors and BPDE - DNA adducts could affect Treg differentiation,which are probably the reasons for the formation of allergic diseases.

Interferon-γ (IFN-γ), a key effector molecule in anti-tumor immune response, has been well documented to correlate with the intratumoral infiltration of immune cells. Of interest, however, a high level of IFN-γ has been reported in salivary adenoid cystic carcinoma (SACC), which is actually a type of immunologically cold cancer with few infiltrated immune cells. Investigating the functional significance of IFN-γ in SACC would help to explain such a paradoxical phenomenon. In the present study, we revealed that, compared to oral squamous cell carcinoma cells (a type of immunologically hot cancer), SACC cells were less sensitive to the growth-inhibition effect of IFN-γ. Moreover, the migration and invasion abilities of SACC cells were obviously enhanced upon IFN-γ treatment. In addition, our results revealed that exposure to IFN-γ significantly up-regulated the level of programmed death ligand 1 (PD-L1) on SACC cell-derived small extracellular vesicles (sEVs), which subsequently induced the apoptosis of CD8⁺ T cells through antagonizing PD-1. Importantly, it was also found that SACC patients with higher levels of plasma IFN-γ also had higher levels of circulating sEVs that carried PD-L1 on their surface. Our study unveils a mechanism that IFN-γ induces immunosuppression in SACC via sEV PD-L1, which would account for the scarce immune cell infiltration and insensitivity to immunotherapy.
B7-H1 Antigen/metabolism* ; CD8-Positive T-Lymphocytes/pathology* ; Carcinoma, Adenoid Cystic/pathology* ; Carcinoma, Squamous Cell/pathology* ; Cell Line, Tumor ; Humans ; Immunosuppression Therapy ; Interferon-gamma/pharmacology* ; Mouth Neoplasms/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Salivary Gland Neoplasms/pathology*