Modulation of Regulatory T-cell Subsets in Very Long-term Treated Aviremic HIV(+) Patients and Untreated Viremic patients

Naïve, central- and effector-like memory regulatory T cells (Tregs) were evaluated in untreated and long-term antiretroviral-treated HIV+ patients that showed comparable CD4+ cell levels, while being, respectively, viremic and aviremic. In the untreated patients, the percentage of naïve-like Tregs was significantly increased to the detriment of central memory regulatory T cells. This redistribution of regulatory Treg subsets may contribute to explain the partially preserved CD4+ cell counts seen in these patients despite the ongoing viremia. On the contrary, in the long-term treated patients, the percentages of Treg subsets were similar to those of healthy donors, demonstrating a restored Treg homeostasis. The characterization of Treg subsets, rather than an evaluation of the total Treg population, may lead to a deeper understanding of the Treg role in HIV infection and therapy

MxA RNA Quantification in Febrile Patients Who Underwent Hematopoietic Cell Transplantation for Primary Immunodeficiency

The presence of myxovirus resistance protein A (MxA) RNA was studied in 55 febrile children with primary immunodeficiency, 27 of whom underwent hematopoietic cell transplantation, and in 28 age-matched controls. The level of MxA RNA was above the cutoff, established as the 95th percentile found in controls, with primary immunodeficiency either undergoing transplantation or not in febrile patients, and with a documented diagnosis of infection by adenovirus, cytomegalovirus, Epstein-Barr virus, respiratory syncytial virus, and rotavirus. The presence of rare viral infections, unrecognized among those that more frequently occur in patients with primary immunodeficiency and in patients undergoing transplantation, may explain the high MxA RNA levels observed in some patients with fever but undetectable genomes or antibodies for the more common viruses. The level of MxA in febrile patients with acute graft versus host disease was below the cutoff, with a median level comparable with that observed in patients with primary immunodeficiency, who did not undergo transplantation and were without fever and infections, but significantly lower compared with controls. The level of MxA was well correlated with viral infections in follow-up samples. These data indicate that the measurement of MxA RNA is simple and useful to detect viral infections and in distinguishing them from acute graft versus host disease after allogeneic cell transplantation

Quantification of newly produced B and T lymphocytes in untrated chronic lymphocytic leukemia patients

BACKGROUND: The immune defects occurring in chronic lymphocytic leukemia are responsible for the frequent occurrence of infections and autoimmune phenomena, and may be involved in the initiation and maintenance of the malignant clone. Here, we evaluated the quantitative defects of newly produced B and T lymphocytes. METHODS: The output of B and T lymphocytes from the production and maturation sites was analyzed in chronic lymphocytic leukemia patients and healthy controls by quantifying kappa-deleting recombination excision circles (KRECs) and T-cell receptor excision circles (TRECs) by a Real-Time PCR assay that simultaneously detects both targets. T-lymphocyte subsets were analyzed by six-color flow cytometric analysis. Data comparison was performed by two-sided Mann-Whitney test. RESULTS: KRECs level was reduced in untreated chronic lymphocytic leukemia patients studied at the very early stage of the disease, whereas the release of TRECs+ cells was preserved. Furthermore, the observed increase of CD4+ lymphocytes could be ascribed to the accumulation of CD4+ cells with effector memory phenotype. CONCLUSIONS: The decreased number of newly produced B lymphocytes in these patients is likely related to a homeostatic mechanism by which the immune system balances the abnormal B-cell expansion. This feature may precede the profound defect of humoral immunity characterizing the later stages of the disease

The different extent of B and T cell immune reconstitution after hematopoietic stem cell transplantation and enzyme replacement therapies in SCID patients with adenosine deaminase deficiency

The lack of adenosine deaminase (ADA) leads to the accumulation of toxic metabolites, resulting in SCID. If the disease is left untreated, it is likely to have a fatal outcome in early infancy. Because hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy with pegylated bovine ADA (PEG-ADA) are both provided in our hospital, we undertook a retrospective longitudinal comparative study of the extent of lymphocyte recovery in two groups of treated ADA-SCID children. Together with classical immunological parameters, we quantified the output of the new B and T cells from the production sites using the κ-deleting recombination excision circle and TCR excision circle assay, and we monitored T cell repertoire diversification. We found that immune reconstitution was different following the two treatments. The stable production of κ-deleting recombination excision circle(+) lymphocytes sustained an increase in B cell number in HSCT-treated patients, whereas in PEG-ADA-treated patients, it was accompanied by a significant and progressive decrease in circulating CD19(+) lymphocytes, which never reached the levels observed in age-matched children. The mobilization of TCR excision circle(+) cells, though lower than in controls, was stable with time after HSCT treatment, leading to a constant peripheral T cell number and to the diversification of the T cell repertoire; however, it was compromised in children receiving prolonged PEG-ADA therapy, whose T cells showed progressively narrowing T cell repertoires

Dimethyldiselenide and diethyldisulphide as novel Se and S precursors for the low temperature MOVPE of ZnSe, ZnS and ZnSSe

The low-temperature pyrolytic MOVPE growth of ZnSe, ZnS and ZnSxSe1-x is reported by using a novel class of VI-group precursors of the form R2X2 (where X = S, Se and R = ethyl, methyl) along with dimethylzinc:triethylammine. Dimethyldiselenide and diethyldisulphide allow the growth below 400°C, i.e. at temperatures reduced by about 150°C with respect to alkyls of the form R2X. The lower thermal stability of these novel precursors is ascribed to a weakening of the X-C bonds in the R2X2 molecule induced by the stronger X-X bond. ZnSe and ZnS growth is thermally activated at low temperatures, the activation energies of both processes being around 29.7 kcal/mol. H was detected in undoped ZnSe at concentrations around (1-3)x10^(17) cm^(-3), along with unintentional N ranging between 8.6x10^(16) and 1.4x10^(18) cm^(-3). Cl and I were also present at around 6x10^(15) cm^(-3) and less than or equal to 1x10^(15) cm?(-3), respectively. 10 K cathodoluminescence (CL) spectra of ZnSe and ZnS show both near-band edge and deep centre emissions, but in the CL spectra of thin ZnSe samples the Y0-line dominates, a clear signature that dislocations occur into these layers

Opposite effects of interferon-beta on new B and T cells release from production sites in multiple sclerosis patients

The release of newly produced B and T lymphocytes from the production sites was analyzed in 30 multiple sclerosis patients treated with interferon-beta by measuring T-cell receptor excision circles and k-deleting recombination excision circles. We found that the therapy induces opposite effects on B- and T-cell mobilization in 33% of patients. New B-cell production, which peaks after 6 months of therapy and then decreases to levels that, however, are still higher than in controls, may cause a renewal of the B-cell compartment. On the contrary, the decreased number of newly produced T lymphocytes observed at 12 months of treatment and the association between reduced thymic output and low peripheral T lymphocytes can be a cause of leukopenia, a frequent side effect of the therapy