Background-Recent studies have suggested that a restrictive pattern assessed with a single spirometry is associated with increased morbidity and mortality. In this study, we sought to determine demographic, clinical, and mortality profiles of subjects with either a recurrent or inconsistent restrictive spirometric pattern assessed prospectively.

Helios, an Ikaros family transcription factor, is preferentially expressed at the mRNA and protein level in regulatory T cells. Helios expression previously appeared to be restricted to thymic-derived Treg. Consistent with recent data, we show here that Helios expression is inducible in vitro under certain conditions. To understand phenotypic and functional differences between Helios+ and Helios− Treg, we profiled cell-surface markers of FoxP3+ Treg using unmanipulated splenocytes. We found that CD103 and GITR are expressed at high levels on a subset of Helios+ Treg and that a Helios+ Treg population could be significantly enriched by FACS sorting using these two markers. Quantitative real-time PCR (qPCR) analysis revealed increased TGF-β message in Helios+ Treg, consistent with the possibility that this population possesses enhanced regulatory potential. In tumor-bearing mice, we found that Helios+ Treg were relatively over-represented in the tumor-mass, and BrdU studies showed that, in vivo, Helios+ Treg proliferated more than Helios− Treg. We hypothesized that Helios-enriched Treg might exert increased suppressive effects. Using in vitro suppression assays, we show that Treg function correlates with the absolute number of Helios+ cells in culture. Taken together, these data show that Helios+ Treg represent a functional subset with associated CD103 and GITR expression.

Background Previous studies on the relation of chronic bronchitis to incident airflow limitation and all-cause mortality have provided conflicting results, with positive findings reported mainly by studies that included populations of young adults. We sought to determine whether having chronic cough and sputum production in the absence of airflow limitation is associated with onset of airflow limitation, all-cause mortality, and serum levels of CRP and IL-8, and whether subjects’ age influences these relations. Methods We identified 1412 participants in the long-term Tucson Epidemiological Study of Airway Obstructive Disease who at enrollment (1972–73) were 21–80 years old and had FEV1/FVC≥70% and no asthma. Chronic bronchitis was defined as cough and phlegm production on most days for ≥three months in ≥two consecutive years. Incidence of airflow limitation was defined as the first follow-up survey with FEV1/FVC<70%. Serum IL-8 and CRP levels were measured in cryopreserved samples from the enrollment survey. Results After adjusting for covariates, chronic bronchitis at enrollment increased significantly the risk for incident airflow limitation and all-cause mortality among subjects <50 years old (Hazard Ratios, 95% CI: 2.2, 1.3–3.8; and 2.2, 1.3–3.8; respectively), but not among subjects ≥50 years old (0.9, 0.6–1.4; and 1.0, 0.7–1.3). Chronic bronchitis was associated with increased IL-8 and CRP serum levels only among subjects <50 years old. Conclusions Among adults <50 years old, chronic bronchitis unaccompanied by airflow limitation may represent an early marker of susceptibility to the effects of cigarette smoking on systemic inflammation and long-term risk for chronic obstructive pulmonary disease and all-cause mortality.

Summary We studied viral evolution in five HLA-B*57 patients recently infected with HIV-1. Escape mutations in HLA-B*57-restricted Gag epitopes were present at study entry in all patients but were not associated with significant increases in viremia. Conversely, no new escape mutations in HLA-B*57-restricted epitopes or known compensatory mutations were detected in patients who experienced significant increases in viremia. Thus the development of escape mutations alone does not determine virologic outcome in recently infected HLA-B*57 patients.

Elite controllers or suppressors (ES) are HIV-1-infected patients who maintain viral loads of <50 copies/ml without antiretroviral therapy. While HLA-B*57 and B*5801 alleles are overrepresented in ES, many HLA-B*57/ B*5801 patients become chronic progressors (CP). We show here that HIV-1 infection results in similar levels of downregulation of HLA-B*57 and HLA-B*5801 molecules on primary CD4 þ T cells from ES and CP. Thus, differences in HIV-1-mediated downregulation of HLA-B*57/B*5801 molecules do not distinguish ES from CP.