Immune response failure against hepatitis C virus (HCV) has been associated with an increased regulatory T cell (Treg) activity. After liver transplantation (LT), 80% of patients experience an ...accelerated progression of hepatitis C recurrence. The aim of this work was to assess the involvement of Tregs, T helper (Th) 1, 2 and 17 cells in recurrent hepatitis C.
Peripheral blood cells obtained before and one month after LT from 22 recipients were analysed. Forty-four key molecules related to Treg, Th1, 2 and 17 responses, were evaluated using qRT-PCR. Liver recipients were classified in two groups according to graft fibrosis evaluated by the METAVIR score on the biopsy performed one year after LT (mild: F ≤ 1, n = 13; severe: F > 1, n = 9). Patients developing a severe recurrence were compared with patients with a mild recurrence.
mRNA levels of Treg markers obtained one month after LT were significantly increased in patients with a severe disease course when compared to patients with a mild recurrence. Markers of the Th1 response were elevated in the same group. No differences in the markers determined before LT were observed.
These findings suggest that Treg, induced by a multifactorial process, which could include a strong Th1 response itself, may play a role in suppressing the early antiviral response, leading to a severe recurrence of hepatitis C.
Introduction Exosomes are nanovesicles found in large quantities in biological fluids and tumors of patients with nasopharyngeal carcinoma (NPC). These tumor exosomes play an important role in tumor ...progression due to their immunosuppressive properties. In addition, it has been reported that the frequency and suppressor functions of CD4 + CD25highFOXP3 + CD127low regulatory T cells (Treg) are also higher in NPC patients than healthy donors. Interactions between NPC-derived exosomes and Treg remain unknown. Here we investigated their ability to induce, expand, activate and recruit human Treg. Material and methods Treg recruitment by exosomes derived from NPC cell lines (C15/C17-Exo), exosomes isolated from NPC patients’ plasma (Patient-Exo), and CCL20 was tested in vitro using Boyden chamber assays and in vivo using a xenograft SCID mouse model ( N = 5), both in the presence and absence of anti-CCL20 monoclonal antibodies (mAb). Impact of these NPC exosomes (NPC-Exo) on Treg phenotype and function was determined using adapted assays (FACS, Q-PCR, ELISA and MLR). Experiments were performed in comparison with exosomes derived from plasma of healthy donors (HD-Exo). Results CCL20 allowed the intra-tumoral recruitment of human Treg. NPC-Exo also facilitated Treg recruitment (3.30 ± 0.34-fold increase, P < .001), which was statistically significantly inhibited ( P < .001) by an anti-CCL20 blocking mAb. NPC-Exo also recruited conventional CD4 + CD25- T cells and mediated their conversion into inhibitory CD4 + CD25high cells. Moreover, NPC-Exo statistically significantly enhanced ( P = 0.0048) the expansion of human Treg, inducing the generation of Tim3Low Treg with increased expression of CD25 and FOXP3. Finally, NPC-Exo induced an overexpression of cell markers associated with Treg phenotype, properties and recruitment capacity. For example, GZMB mean fold change was 21.45 ± 1.75. These results were consistent with a stronger suppression of responder cells’ proliferation ( P < .001), and the secretion of immunosuppressive cytokines (IL10, TGFB1). Conclusion Interactions between NPC-Exo and Treg represent a newly defined mechanism that may be involved in regulating peripheral tolerance by tumors and in supporting immune evasion in human NPC.
A retrospective radiologic analysis of Paget's disease of the spine.
The prevalence, anatomic distribution, mechanisms of formation of Pagetic vertebral ankylosis (PVA) and the possibility of a ...relationship to diffuse idiopathic skeletal hyperostosis (DISH) were assessed in a large population of persons with Paget's disease.
Acquired vertebral ankylosis is not a common feature of the Paget's disease of the spine and its mechanisms of formation remain unknown. In some reports, PVA was associated with radiographic signs of DISH.
Of 337 Pagetic patients monitored in the Division of Rheumatology from 1961 to 1990, all 245 who had entire spine radiographs were selected for study. Radiographs were studied for signs of Pagetic vertebral lesions and for spinal lesions of DISH.
The study group contained 156 men with a mean age of 68 years (range 37-92) and 89 women with a mean age of 71 years (range 50-89). Fourteen PVA were observed on the radiographs of 11 men (mean age 68 years; range 60-76). One PVA was cervical, eight were thoracic, one thoracolumbar, three lumbar, and one lumbosacral. Eighty of the two hundred forty-five patients (32.6%) had characteristic features of DISH. Eight out of the eleven patients with PVA also had evidence of spinal lesions of DISH and radiographic features of DISH were observed contiguous to ten of the fourteen PVA.
The scarcity of PVA reported in the literature and in our study (4.4% of 245 patients) suggests that constant progression of the disease from one vertebra to another by invasion of intervertebral disc space is rare. However, the higher incidence of PVA in men, their preferential location at the thoracic spine and their association with lesions of DISH suggest that progression of Pagetic lesions by invasion of bridging osteophytes may be an important mechanism for the intervertebral spread of Paget's disease.
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