Administration of IL-2 to HIV-infected patients leads to expansion of a unique subset of CD4 + CD45RO -CD25 + cells. In this study, the origin, clonality, and function of these cells were investigated. Analysis of TCR excision circles revealed that the CD4 + CD45RO -CD25 + cells were the product of peripheral expansion but remained polyclonal as determined by TCR repertoire analysis. Phenotypically, these cells were distinct from naturally occurring Tregs; they exhibited intermediate features, between those of memory and naive cells, and had lower susceptibility to apoptosis than CD45RO -CD25 -or memory T cells. Studies of intracellular cytokine production and proliferation revealed that cytokine-expanded naive CD25 + cells had low IL-2 production and required costimulation for proliferation. Despite elevated expression of forkhead transcription factor P3 (foxP3), they exerted only weak suppression compared with CD45RO + CD25 +high cells (Tregs). In summary, in vivo IL-2 administration to HIV-infected patients leads to peripheral expansion of a population of longlived CD4 + CD45RO -CD25 + cells that express high levels of foxP3 but exert weak suppressive function. These CD4 + CD25 + cytokine-expanded naive cells, distinct from antigen-triggered cells and Tregs, play a role in the maintenance of a state of low turnover and sustained expansion of the CD4 + T cell pool.
Uric acid, an important scavenger of ozone, has been identified as the major low molecular weight antioxidant in baseline and cholinergically induced nasal secretions. The purpose of this study was to determine the specific tissue source of uric acid in airway secretions. The secretion of uric acid is increased by cholinergic stimulation and correlates closely with the secretion of lactoferrin (a nasal glandular protein), suggesting that submucosal glands are involved. Indeed, nasal turbinate tissue was found to contain uric acid. However, careful analysis of nasal turbinate tissue failed to reveal the presence of xanthine oxidase, the enzyme responsible for uric acid synthesis. These data suggest that uric acid might be taken up secondarily by glands from plasma. This possibility was strengthened by the observation that lowering the plasma urate level with probenecid concomitantly lowered urate secretion. These findings are consistent with the hypotheses that the principal source of uric acid in nasal secretions is plasma and that uric acid is taken up, concentrated, and secreted by nasal glands.
Pneumocystis carinii pneumonia (PCP) can be diagnosed by direct microscopic examination of induced sputum or by bronchoalveolar lavage (BAL). However, many institutions have little diagnostic success with induced sputum, and BAL is invasive and expensive. This prospective, blinded study assessed oral washes as a more convenient specimen than either sputum or BAL fluid and used a dissociation-enhanced lanthanide fluoroimmunoassay time-resolved fluorescent hybridization polymerase chain reaction (PCR) detection system that is feasible for clinical laboratories. The study assessed 175 oral washes, each paired with either an induced sputum that was positive for Pneumocystis or a BAL sample. The PCR test based on the Pneumocystis major surface glycoprotein primers had a sensitivity of 91% and a specificity of 94%, compared with a test based on mitochondrial large subunit rRNA primers, which had a sensitivity of 75% and a specificity of 96%. These results suggest that oral washes can provide a useful sample for diagnosis of PCP when a sensitive PCR detection system is used.
Abnormal fluorodeoxyglucose accumulation occurs in the nodes of individuals with detectable viral loads. Interruption of effective HAART results in the activation of previously quiescent nodal areas.
Abnormal FDG accumulation occurs in nodes of subjects with detectable viral loads. Interruption of effective ART results in activation of previously quiescent nodal areas.
The pharmacokinetics of thalidomide in nine human immunodeficiency virus-infected patients were studied. Single doses of thalidomide were well absorbed, with mean peak concentrations (+/- standard deviations) of 1.17 +/- 0.21 and 3.47 +/- 1.14 microg/ml in the 100- and 300-mg dosing groups, respectively, and the mean elimination half-life was approximately 6 h. Adverse effects were mild, with drowsiness being reported for seven of nine patients.
Studies establishing that intermittent subcutaneous interleukin-2 (IL-2) therapy can lead to substantial CD4 cell increases in many HIV-infected patients have generally been of limited duration. We studied 77 patients participating in active longitudinal studies of subcutaneous IL-2 therapy at our center in order to determine the long-term feasibility of this approach. Following initial induction, patients in each trial were eligible to receive intermittent 5-day cycles of subcutaneous IL-2 treatment at individualized doses and frequencies capable of maintaining CD4 counts at postinduction levels. The mean duration of study participation to date is 5.9 years (range, 1.0-9.3 years). Mean baseline CD4 cell count and CD4 percent values of 0.521 ؋ 10 9 /L (521 cells/ L) and 27% have risen to 1.005 ؋ 10 9 /L (1005 cells/L) and 38%, respectively, at 90 months. The mean number of subcutaneous IL-2 cycles required to achieve and maintain these increases was 10 cycles (range, 3-29 cycles), and the current mean interval of cycling required to maintain these elevations is 39 months (median, 35 months; range, 2-91 months). We conclude that subcutaneous IL-2 therapy is capable of maintaining CD4 cell increases for an extended period using a remarkably low frequency of intermittent cycling. These observations may contribute to patients' acceptance of subcutaneous IL-2 as a favorable long-term treatment strategy. (Blood. 2004;103:3282-3286)
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