A Decreased Frequency of Regulatory T Cells in Patients with Common Variable Immunodeficiency

Introduction: Common variable immunodeficiency disorder (CVID) is a heterogeneous syndrome, characterized by deficient antibody production and recurrent bacterial infections in addition abnormalities in T cells. CD4(+)CD25(high) regulatory T cells (Treg) are essential modulators of immune responses, including down-modulation of immune response to pathogens, allergens, cancer cells and self-antigens.Objective: in this study we set out to investigate the frequency of Treg cells in CVID patients and correlate with their immune activation status.Materials and Methods: Sixteen patients (6 males and 10 females) with CVID who had been treated with regular intravenous immunoglobulin and 14 controls were enrolled. Quantitative analyses of peripheral blood mononuclear cells (PBMC) were performed by multiparametric flow cytometry using the following cell markers: CD38, HLA-DR, CCR5 ( immune activation); CD4, CD25, FOXP3, CD127, and OX40 (Treg cells); Ki-67 and IFN-gamma (intracellular cytokine).Results: A significantly lower proportion of CD4(+)CD25(high) FOXP3 T cells was observed in CVID patients compared with healthy controls (P<0.05). in addition to a higher proportion of CD8(+) T cells from CVID patients expressing the activation markers, CD38(+) and HLA-DR(+) (P<0.05), we observed no significant correlation between Tregs and immune activation.Conclusion: Our results demonstrate that a reduction in Treg cells could have impaired immune function in CVID patients.Universidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Resident acquisition of knowledge during a noontime conference series.

BACKGROUND AND OBJECTIVES: Noontime conferences are widely used in family practice residencies. This study determined the effectiveness of noontime conferences for increasing residents\u27 knowledge. METHODS: Twenty residents were tested monthly over 6 months and then cumulatively on the content of noontime conferences. RESULTS: Monthly test scores of attendees versus nonattendees were compared using a two-sample, two-tail t test. Results revealed the mean score of attendees for short-term knowledge to be 12.1 points higher than nonattendees. There was no correlation, however, between conference attendance and long-term knowledge retention. CONCLUSIONS: Our findings indicate a lack of correlation between noontime conference attendance and long-term cumulative test scores. The results question the value of noontime conferences as a teaching method

Elevated Frequency of Gamma Interferon-Producing NK Cells in Healthy Adults Vaccinated against Influenza Virus▿

Recent studies indicate that innate immunity in influenza virus infection is an area of substantial importance for our understanding of influenza virus pathogenesis, yet our knowledge of the mechanisms controlling innate immunity remains limited. Further delineation of the roles of NK cells and innate immunity in viral infection may have important implications for the development of improved influenza virus vaccines. In this study, we evaluated the phenotype and function of NK and T lymphocytes, as well as influenza virus-specific immunoglobulin G production, prior to and following vaccination with the routinely administered trivalent influenza virus vaccine. We demonstrate influenza virus antigen-specific innate and adaptive cellular responses and evaluate changes in NK cell receptor expression over time. Our results demonstrate increased innate and adaptive cellular immune responses and show that NK cells are a significant source of gamma interferon (IFN-γ) following influenza virus vaccination. An increase in the frequency of IFN-γ-producing NK cells was observed in many subjects postvaccination. The subset distribution with respect to CD56dim and CD56bright NK cell subsets remained stable, as did the NK cell phenotype with respect to expression of cell surface activating and inhibitory receptors. These results may form the basis for further investigations of the role of NK cells in immunity to influenza

Comparison of Treg cell subsets between healthy controls (CTL) and CVID patients.

<p>In CVID group there was a significant lower percentage of FOXP3⁺CD25^highCD127^lowCD4⁺ T cell (<i>P</i> = 0.0034).</p

Flow cytometric panels showing the gating strategy from healthy and CVID patients.

<p>(A) The gate is set around the population of lymphocytes; (B) CD3 T cells that were evaluated for (C), FOXP3, CD25; (D) Side scatter and CD3⁺FOXP3⁺CD25^highCD127^low. (E) The gate is set around the population of FOXP3+CD25^highCD127^lowCD4⁺ T cells. Fluorescence minus one was used to define the gate used. Arrows indicate the gated population subsequently analyzed.</p

Comparisons of CD8⁺CD38⁺ (A), CD8⁺HLA-DR⁺ (B) and CD8⁺CD38⁺CCR5⁺ (C) T cell percentages in PBMC in healthy controls (CTL) and CVID patients showing significant difference in the activation.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006269#pone-0006269-g001" target="_blank">Figure 1A</a>-, <i>P</i> = 0.002; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006269#pone-0006269-g001" target="_blank">Figure 1B</a>-, <i>P</i> = 0.008; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006269#pone-0006269-g001" target="_blank">Figure 1C, <i>P</i></a> = 0.021.</p

Clinical and laboratory characteristics of studied subjects.

<p>IQR: Inter -quartile range.</p

Vital staining of the stick insect digestive system identifies appendices of the midgut as novel system of excretion.

The stick insects or phasmids (Phamsatodea) have a series of pyriform ampulles with long, thin filaments on the posterior end of their midgut referred to as the "appendices of the midgut." Found only in phasmids, their function had never been determined until now. Their similarity to the Malpighian tubules, which are ubiquitous insect organs of excretion, suggested a similar function. To differentiate between the appendices and the Malpighian tubules and compare functional differences between the two tissue types, vital staining (the injection of histological stains into living organisms) was done in conjunction with light and scanning electron microscopy in multiple phasmid species. The results showed that the appendices originated in the basal phasmids (Timematidae) and grew more numerous in derived species. The appendices stain selectively, notably failing to pick up the indicators of the two known systems of invertebrate excretory function, indigo carmine and ammonium carmine. Appendices sequester stains in the ampule portion before eliminating the compounds into the midgut. We conclude by confirming that the appendices do have an excretory function, but one unlike any other known in invertebrates. Their function is likely cation excretion, playing a role in calcium regulation and/or organic alkaloid sequestration. The appendices must thus be considered distinct organs from the Malpighian tubules