CD4 1 CD25 hi CTLA4 1 FoxP3 1 regulatory T cells (Treg) have been shown to maintain immune tolerance against self antigens and increased circulating frequencies have been reported in various types of cancers. Circulating invariant natural killer T-cells (iNKT) are reduced in cancer patients and low iNKT frequency is related to poor prognosis. It is not yet clear whether high Treg numbers and low iNKT cell numbers pose an increased risk for the progression of premalignant lesions or whether Treg and iNKT cell numbers are influenced by dysplasia. We therefore studied prospectively the relation between iNKT cell and Treg frequencies and the natural course of human papillomavirus type 16 (HPV16) induced pre-malignant cervical dysplasia in 82 patients who participated in a nonintervention cohort study of women with abnormal cytology. Treg frequencies were significantly increased in women who had persistent HPV16 infection. Within the HPV16 persistence group there was no difference in Treg frequencies among patients who developed a CIN3 lesion and patients who did not progress to CIN3. Furthermore, Treg frequencies were increased in patients who had detectable HPV16 E7 specific IL-2 producing T-helper cells, which suggests a causal role of HPV infection in Treg development in parallel with HPV16 specific T helper cells. No evidence was found for a role for iNKT cells in persistence of HPV16 and progression of HPV16 induced CIN lesions. However, HPV-persistence-associated Tregs may explain the inefficacy of concomitant persistence associated immunity and may contribute to subsequent progression to neoplasia. ' 2007 Wiley-Liss, Inc.Key words: regulatory T cells; invariant NKT cells; HPV type 16; persistence; CIN Specific immune responses against viruses and cancer are controlled by various regulatory cells. This negative regulation occurs by naturally occurring CD4 1 CD25 hi regulatory T cells (Tregs), induced antigen specific regulatory T-cells (Tr1 and TH3 cells) or CD4 1 CD25 hi cells developing from CD4 1 CD25 2 T-cells. Unlike naturally occurring Tregs, which can be identified by intracellular cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and forkhead box (Fox)P3 expression, antigen specific regulatory T-cells have no discriminating phenotype. 1-3 Increased numbers of circulating Tregs have been detected in patients with solid tumors 4 and hematologic malignancies. 5 While there is evidence for an influence of tumor associated factors, 6 it has also been suggested that an age related increase in Treg frequencies is associated with an increased risk to develop cancer. 7 Another regulatory T cell is the invariant natural killer T (iNKT) cell, which is characterized by expression of the Va24Vb11 invariant T-cell receptor and NK cell receptors. iNKT cells have the capacity to either enhance or suppress immuneresponses by secreting proinflammatory or anti-inflammatory cytokines respectively upon activation via antigenic recognition of the glycolipid a-galactosylceramide (a-GalCer) in the context of the non-polymo...

No abstract

The prevalence of celiac disease (CD) in patients with type 1 diabetes mellitus (T1DM) is 4.5 %. Objective of the study is to investigate (1) the course of glycemic control at CD diagnosis and after the initiation of a gluten-free diet (GFD) in T1DM patients; (2) the prevalence of diabetic complications in T1DM patients with adult onset of CD. In 20 hospitals in the Netherlands, we identified T1DM patients diagnosed with CD at adult age. We retrospectively collected glycated hemoglobin (HbA1c) levels before CD diagnosis, at CD diagnosis, and the most recent HbA1c levels as well as the presence of nephropathy and retinopathy. The control group consisted of patients with T1DM and negative CD serology matched for age, gender, T1DM duration, and HbA1c levels. Thirty-one patients were eligible with a median duration of T1DM and CD of 27 years (IQR 14-37) and 3 years (IQR 1-8), respectively. The matched control group consisted of 46 patients. HbA1c levels at the moment of CD diagnosis were 7.5 % (IQR 7.1-8) [58 mmol/mol] and at the most recent visit 7.4 % (IQR 6.9-7.9, P = 0.15) [57 mmol/mol] indicating no difference. Prevalence of retinopathy was lower in T1DM + CD group compared with controls, (38.7 vs 67.4 %, P < 0.05), whereas no difference in the prevalence of nephropathy was found between the groups (P = 0.09). In conclusion, T1DM + CD patients have less retinopathy compared to T1DM patients without CD. A GFD possibly favorable affects the development of vascular complications in T1DM patients.

Carbon dioxide used for abdominal insufflation seems to limit the postoperative inflammatory response and to preserve parameters reflecting the immune status. These findings may be of importance in determining the preferred method of laparoscopy in oncologic surgery.

Development of tolerance to gluten seems possible in some patients with CD. Further follow-up will show whether this tolerance is permanent or only a long-term return to latency. This feature may be associated with genetic characteristics, especially with HLA genotypes that differ from DQ2 or DQ8. More insight into the mechanisms of the development of gluten tolerance may help to distinguish those CD patients that might not require life-long GFD.