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Background: Little is known about the pathogenesis of scleromyxedema, a life‐threatening fibromucinosis disease with immunological dysregulation. Objectives: To investigate on T‐cell phenotype, function and cytokine biology in search of new insights supporting the immunopathogenesis of the disease. Methods: We analysed the frequency of circulating lymphocyte subsets, the T‐cell maturation stage, the generation of antigen‐specific T‐cell lines and T‐cell cytokine secretion. Results: The analysis of T‐cell maturation stage and the TCR spectratyping findings revealed that scleromyxedema patients showed clear immunological signs of long‐lasting immune system activation and stimulation leading to a skewed T‐cell repertoire. Moreover, these analyses showed that both CD4+ and CD8+ T cells from scleromyxedema patients have a profound deficiency (even after stimulation) relatively to the production of IFN‐γ and IL17 with respect to healthy donor control cells, while they are massively skewed towards IL4 secretion after stimulation. Conclusions: Our data indicate that a chronic Th2‐skewed T‐cell response against an unknown target antigen leading to abnormally high IL4 secretion, a pro‐fibrotic cytokine, is a main immunological hallmark of scleromyxedema patients. These results, never reported before, may have a translational therapeutic value due to the availability of anti‐IL4 agents such as dupilumab. [ABSTRACT FROM AUTHOR]

Recent studies on regulatory lymphocytes demonstrate that CD8+ T suppressor (Ts) cells may have great relevance in controlling immune system homeostasis and avoiding development of chronic inflammatory diseases. Among the three subpopulations of CD8+ Ts cells so far recognized in humans, the type 2 (non-antigen-specific) cell is characterized by the capacity to inhibit both T cell proliferation and cytotoxic T lymphocyte activity through secretion of soluble factors. Previous work has shown the impairment of in vitro generation of type 2 CD8+ Ts cells from the peripheral blood of relapsed patients with multiple sclerosis, systemic lupus erythematosus, or systemic sclerosis. Here, similar findings are demonstrated for patients with human immunodeficiency virus or chronic hepatitis C virus infection. Furthermore, the presence of type 2 CD8+ Ts cells infiltrating diseased tissues in patients with autoimmune thyroiditis or cancer is shown. Collectively, these findings suggest that type 2 CD8+ Ts cells may be involved in the control of pathologic chronic immune responses, contributing in some cases to the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Background: The immunomodulatory effects of allogeneic blood transfusion may contribute to a poor prognosis in patients with cancer who are undergoing surgery, and clinical trials have been carried out to investigate whether these patients would benefit from autologous blood donation. As the immunomodulatory effects of allogeneic blood transfusion have been related to soluble molecules released from residual WBCs during storage, the in vitro immunomodulatory activity of soluble molecules detected in supernatants from stored autologous blood was evaluated.Study Design and Methods: Blood was donated by four healthy volunteers. Packed WBC-reduced RBCs were obtained and stored for 30 days, and supernatants were collected. FFP and serum were also obtained. The concentration of soluble molecules was determined by immunoenzymatic assays. The in vitro immunomodulatory activity of undiluted blood component supernatant was assessed by antigen-specific cytotoxic T-cell activity and mixed lymphocyte reactions in autologous combinations and by apoptosis induction in Fas+ cells.Results: The concentrations of soluble Fas-ligand and HLA class I molecules were higher in packed RBCs than in WBC-reduced RBCs, FFP, and serum. Undiluted supernatants of packed RBCs strongly inhibited functional assays and induced apoptosis in Fas+ cells. The immunomodulatory effects were correlated with the amount of soluble Fas ligand and HLA class I molecules.Conclusion: The results of the present study are comparable with those already reported in allogeneic blood components, and they indicate that undiluted supernatants of autologous blood components may exert immunosuppressive effects in vitro. [ABSTRACT FROM AUTHOR]

Besides being present in serum in association with β2-μ, HLA class I heavy chains are also present in serum as β2-μ-free moieties. The increase in serum levels of β2-μ-associated HLA class I heavy chains in conditions associated with an activation of the immune system have prompted us to measure the serum levels of β2-μ-free HLA class I heavy chains in the course of immune responses to viral antigens and to mismatched histocompatibility antigens. The serum level of β2-μ-free HLA class I heavy chains, like that of β2-μ-associated HLA class I heavy chains was significantly increased in patients affected by advanced HIV-1 infection or by chronic hepatitis C (CHC). In the latter group of patients an association was found between a reduction in the β2-μ-free HLA class I heavy chain serum level and response to therapy with interferon a and ribavirin. Moreover, the β2-μ-free HLA class I heavy chain serum level was increased more than that of β2-μ-associated HLA class I heavy chains during episodes of liver ischemia following liver transplantation and in the course of acute graft rejection and of acute graft-versus-host-disease (GVHD) after allogeneic bone marrow transplantation (BMT). These results suggest that the serum levels of β2-μ-free and β2-μ-associated HLA class I heavy chains are independently regulated. Furthermore, β2-μ-free HLA class I heavy chain serum level may be a useful marker to monitor response to therapy in CHC patients and the clinical course of liver and bone marrow grafts. [ABSTRACT FROM AUTHOR]

Purpose of the study Promising research suggest that maraviroc (MVC) has favourable clinical outcome in HIV-infected patients (pts). Aim of the study is to assess: durability, safety profile and immunovirological recovery in a large MVC-based cohort. Methods All HIV pts treated with antiretroviral therapy (ART) containing MVC for at least 6 months (all viruses CCR-5 tropic analyzed by genotypic and phenotypic test) were recruited in an observational multicenter study. Eight Infectious Diseases Centers in Liguria and Piedmont (Italy) collected at baseline and every 3 months demographics, clinical and immunovirological data on a web-based system (by MedinfoDist, University of Genoa). We used SPSS for Pearson Chi square test and for generalized estimating equation (GEE); in this model for longitudinal data and frequency analysis we considered altered: TCD4+≤350/mmc, HIVRNA>50 cp/ml, total cholesterol >200 mg/dl, triglycerides >160 mg/dl, transaminase>40 mg/dl, creatinine>1.3 mg/dl and we divided data in 5 time periods: baseline, 1-6, 9-12, 15-24 and 24-45 months. Summary of results We enrolled 55 pts: 36 (65%) males, median age 49.6 years (yrs) (range [r] 18.2-76.6, IQR 44.5-53.3), 11 (20%) HCVRNA-positive, 4 (7%) HBsAg-positive, 1 both infection. Twenty-four (44%) pts were classified as CDC C stage, median nadir TCD4+ was 219/mmc (r 11-529, IQR 125-317), median duration of ART was 15.3 yrs (r 1.3-27.3, IQR 12-16.8), median duration of treatment with MVC was 23 months (r 6-47, IQR 14-36). At baseline 42 (76%) pts had HIVRNA >50 cp/ml, 11 (20%) HIVRNA≤50 cp/ml, 2 (4%) pts no data; on treatment at the last examination 53 pts (96%) had HIVRNA≤50 cp/ml, 2 pts still had HIVRNA>50 cp/ml (CCR5 tropic) and median TCD4+ count was 469/mmc (r 73-1802, IQR 302-592). One pt died and only 2 pts shifted to X4. Chi square test at 9-12 months showed p=0.0001 and the 80% of pts had TCD4+>350/mmc; at the same observation time 83.3% of pts had HIVRNA ≤50 cp/ml (p=0.0001). About cholesterol, triglycerides, transaminase and creatinine no significative differences were found and the median value showed no changes. Conclusions In our study a majority of pts treated with ART containing MVC achieved a count of TCD4 >350/mmc and HIVRNA undetectable within 9-12 months. This regimen is a safe, feasible option and in pts with a poor immunological stage, MVC offered a remarkable TCD4+ count gain with limited X4 strains onset. [ABSTRACT FROM AUTHOR]

Objective: Ig molecules contain epitopes that can induce T cell-mediated immune responses. B cells can process and present such epitopes and activate T cells. The purpose of the present study was to test our hypothesis that T cells that recognize an Ig consensus sequence presented by B cells will modulate lupus-like disease in mice., Methods: (NZB x NZW)F(1) (NZB/NZW) lupus mice received somatic B cell gene transfer of a DNA plasmid encoding a consensus sequence of T cell determinants of murine anti-DNA IgG or control plasmids. Treated animals were monitored for the production of antibody, the development of renal disease, and the phenotype, number, and function of T cells., Results: Treatment of mice with Ig consensus plasmid induced transforming growth factor beta-producing CD8+,CD28- T cells that suppressed the antigen-specific stimulation of CD4+ T cells in a cell-contact-independent manner, reduced antibody production, retarded the development of nephritis, and improved survival. Significantly, adoptive transfer of CD8+,CD28- T cells from protected mice into hypergammaglobulinemic NZB/NZW mice effectively protected the transferred mice from the development of renal disease., Conclusion: Gene expression of anti-DNA Ig consensus sequence induces immunoregulatory T cells that delay the development of lupus nephritis by suppressing hypergammaglobulinemia and renal disease.