Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function

Interleukin (IL)-21 is the most recently recognized of the cytokines that share the common cytokine receptor gamma chain (gamma(c)), which is mutated in humans with X-linked severe combined immunodeficiency. We now report that IL-21 synergistically acts with IL-15 to potently promote the proliferation of both memory (CD44high) and naive (CD44low) phenotype CD8+ T cells and augment interferon-gamma production in vitro. IL-21 also cooperated, albeit more weakly, with IL-7, but not with IL-2. Correspondingly, the expansion and cytotoxicity of CD8+ T cells were impaired in IL-21R-/- mice. Moreover, in vivo administration of IL-21 in combination with IL-15 boosted antigen-specific CD8+ T cell numbers and resulted in a cooperative effect on tumor regression, with apparent cures of large, established B16 melanomas. Thus, our studies reveal that IL-21 potently regulates CD8+ T cell expansion and effector function, primarily in a synergistic context with IL-15.     

Magnetocardiographic indices of left ventricular hypertrophy

OBJECTIVE: We tested the hypothesis that multichannel magnetocardiographic (MCG) mapping can detect and quantify the degree of left ventricular hypertrophy (LVH). DESIGN: A cross-sectional study. SETTING: Helsinki University Central Hospital, a tertiary referral center. PARTICIPANTS: Forty-two patients with pressure overload induced LVH by gender-specific echocardiographic criteria (LVH group), and 12 healthy middle-aged controls. MAIN OUTCOME MEASURES: MCG QRS-T area integrals and QRS-T angle in magnetic field maps in relation to echocardiographic LVH as well as left ventricular (LV) mass and structure. Conventional 12-lead electrocardiographic (ECG) LVH indices (Sokolow-Lyon voltage, Cornell voltage, Cornell voltage duration product) were assessed for comparison. RESULTS: MCG QRS- and T-wave integrals provided complementary information of echocardiographic LV mass. Their combination, the QRS-T integral, and the QRS-T angle were increased in patients with LVH and, in those patients, correlated significantly with LV mass indexed to body surface area (r = 0.455;P = 0.002 and r= 0.379; P= 0.013, respectively). A QRS-T integral 16000 fT.s had identical sensitivity of 62% at 92% specificity as the gender-adjusted Cornell voltage duration product of 240 micro V.s for the detection of LVH. CONCLUSIONS: The MCG method can detect patients with LVH and also quantify the degree of LVH in patients with increased LV mass.     

Heart rate adjustment of magnetic field map rotation in detection of myocardial ischemia in exercise magnetocardiography

Aims We studied the capability of heart rate (HR) adjusted change in multichannel magnetocardiogram (MCG) to detect exercise-induced ischemia. Methods and results The MCG and 12-lead ECG were recorded simultaneously during supine exercise testing in 17 healthy controls and 24 patients with single vessel coronary artery disease (CAD). In the MCG analysis, we plotted the orientation of the magnetic field map (MFM) against the HR in each cardiac cycle during recovery. A regression line was fitted to the data and the line slope (degrees/bpm) was determined. In the ECG, the ST-segment depression vs HR (ST/HR) slope was evaluated. The HR adjusted MFM rotation was more extensive in the pooled CAD group, and in all subgroups with different stenosed vessel, than in the control group at the ST-segment (1.5 ± 2.1°/bpm vs 0.29 ± 0.25°/bpm, p < 0.0005) and at the T-wave apex (0.95 ± 0.81°/bpm vs 0.24 ± 0.25°/bpm, p < 0.0005). Areas under the receiver operating characteristic curves of the HR adjusted MFM rotation at the ST-segment (88.5 %) and the T-wave (86.0 %) were higher than the ones without HR adjustment (75.5 % and 68.1 %, respectively), and higher than the area of ST/HR slope in the ECG (80.2 %). Conclusion HR adjusted MFM rotation detects transient ischemia independent of the stenosed vessel. HR adjustment improves the performance of the MCG in ischemia detection by the analysis of the ST-segment and the T-wave. The MCG was superior to the 12-lead ECG. Received: 5 April 2001, Returned for 1. revision: 7 May 2001, 1. Revision received: 25 May 2001, Returned for 2. revision: 12 June 2001, 2. Revision received: 18 June 2001, Accepted: 20 June 2001     

Complete avulsion of the splenic vascular pedicle as a birth injury

The survivor of a rare birth injury is reported. The patient was a term girl weighing 5,340 g at birth. At the age of 2 days abdominal symptoms began (vomiting and distenison). At laparotomy at 4 days of age, the spleen was found completely avulsed from its vascular pedicle and was removed. The abdomen was full of blood, but there was no acute bleeding. The postoperative course was uneventful. At re-examination at the age of 3 months she was in good health. To minimize the risk of overwhelming sepsis due to encapsulated bacteria, vaccinations are in progress. Offprint requests to: H. Lindahl