Assessment of selected co-stimulatory, adhesion and activatory molecules and cytokines of Th(1)/Th(2) balance in acute lymphoblastic leukemia in children.

INTRODUCTION: Recent years have seen a rise in the importance of cytokine production and co-stimulatory/activatory molecule expression in the immune response in leukemia. The aim of our study was to assess the function of T lymphocytes in children with acute lymphoblastic leukemia (ALL) during remission induction based on selected cytokine and co-stimulatory/activatory molecule expression. MATERIAL/METHODS: The study group consisted of 50 children with ALL (B cell precursor). Peripheral blood samples were taken before treatment (day 0), after the prednisone prophase (day 8), and during (day 15) and after (day 33) remission induction. The percentages of T cells with interferon (IFN)-gamma (Th(1)), interleukin (IL)-4 (Th(2)) and IL-2 receptor (IL-2R), CD28, CTLA-4, CD38, ICAM-1, and HLA-DR expression were assessed by tricolor flow cytometry. RESULTS: At the time of diagnosis we noted higher percentages of T cells with adhesion molecule ICAM-1, activation molecule CD38 expression, and an increased population of Th(2 )cells (IL-4) compared with the control group. During and after remission induction we observed a decreased population of CD38(+) T cells, elevated percentages of helper T lymphocytes with IL-2R expression, and a rise in helper T lymphocytes producing IFN-gamma (Th(1)). During fever/infection, higher levels of activated T lymphocytes (CD4(+)HLA-DR(+), CD8(+)HLA-DR(+)), a rise in Th1, and no change in Th(2 )populations were observed. CONCLUSIONS: The results suggest T cell activation and Th(2 )predominance at the time of diagnosis and during remission induction in ALL in children. These results confirm the involvement of cellular immunity in the leukemic process and can be used in immune therapy in leukemia.

123I-interleukin-2 scintigraphy for in vivo assessment of intestinal mononuclear cell infiltration in Crohn's disease.

UNLABELLED: Activated mononuclear cells expressing interleukin-2 (IL2) receptors (IL2-Rs) heavily infiltrate the Crohn's disease (CD) gut wall. A new technique for the in vivo detection of tissue infiltrating IL2-R positive (IL2R+ve) cells was developed based on 123I-IL2 scintigraphy. The aim of this study was to investigate whether 123I-IL2 accumulates in the CD gut wall in different phases of the disease and to evaluate the specificity of 123I-IL2 binding to activated IL2R+ve cells infiltrating the gut wall. METHODS: Fifteen patients with ileal CD (10 active and 5 inactive) and 10 healthy volunteers were studied by 123I-IL2 scintigraphy. Six patients with active CD were studied before and after 12 wk of steroid treatment. After scintigraphy, patients were followed up for 29-54 mo. Ex vivo autoradiography was performed to determine specificity of 125I-IL2 binding to IL2R+ve cells. For bowel scintigraphy, 123I-IL2 (75 MBq) was injected intravenously and gamma camera images were acquired after 1 h. Bowel radioactivity was quantified in 64 regions of interest (ROIs). RESULTS: Autoradiography showed specific binding of 125I-IL2 to IL2R+ve mononuclear cells infiltrating the CD gut wall. Intestinal 123I-IL2 uptake assessed by the number of positive ROIs was higher in patients with active or inactive CD than in healthy volunteers (P < 0.0001 and P = 0.03, respectively) and positively correlated with the CD activity index (P = 0.01). 123I-IL2 intestinal uptake significantly decreased in patients with CD in steroid-induced remission (P = 0.03). A significant correlation was observed between the number of positive ROIs and time to disease relapse. CONCLUSION: 123I-IL2 accumulates in the diseased CD gut wall by specific binding to IL2R+ve cells, infiltrating the involved tissues. 123I-IL2 scintigraphy may be an objective tool for the in vivo assessment of intestinal activated mononuclear cell infiltration.

An albumin-coated polyester arterial graft: in vivo assessment of biocompatibility and healing characteristics.

The albumin-coated vascular graft (ACG) and its uncoated polyester substrate, the Vascular II (V-II), were evaluated in terms of biocompatibility and biofunctionality using two in vivo animal studies. Biocompatibility and immunoreactivity were assessed by implanting intraperitoneally in the rat small segments of the ACG and the V-II graft and harvesting them with their surrounding tissue 3d, 1, 2 and 4 weeks later. Cytofluorometric determination of total T cells (CD3), the ratio of CD4/CD8 subsets and the percentage of IL-2 receptor-positive T cells in the peripheral blood has revealed that no significant difference in any of the T cell populations was found between the ACG and the V-II graft. The cellular reactivity of the ACG in terms of acid phosphatase activity at the implant side was significantly greater at 3 d but not at longer periods. Biofunctionality was evaluated by implanting both grafts as a thoracoabdominal vascular bypass in dogs for 11 different periods ranging from 4 h to 6 months. The rate of albumin resorption was such that traces were still present at 1 month, but no longer observable at 2 months. Tissue incorporation into the graft wall was earlier for the V-II (2 weeks) than for the ACG (4 weeks), which showed complete encapsulation, tissue incorporation and endothelialization after 2 months in vivo. Only small differences were observed between both grafts in terms of platelet and fibrin uptake on the luminal surface. The prostacyclin/thromboxane A2 ratio increased to a level higher that 1.0 aorta within 1 month for the V-II and 4 months for the ACG. In conclusion, the Bard ACG has demonstrated excellent biocompatibility in terms of blood T cell behaviour and acid phosphatase activity at the implant site. Finally, its healing response is equivalent to that of the uncoated Dacron prosthesis once the albumin coating has been resorbed.

An assessment of serum and urine soluble interleukin-2 receptor concentrations during renal transplant rejection.

During rejection, renal transplant recipients have increased concentrations of soluble interleukin-2 receptors (sIL-2R) in their serum and urine. However, the clinical application of this measurement in the diagnosis of rejection or the assessment of treatment efficacy is limited by the variance of the measurement in sample populations. We examined the serum and urine sIL-2R concentrations in 20 renal transplant recipients, 12 of whom experienced 13 episodes of allograft rejection. There was no statistical difference in the mean serum sIL-2R concentration at the time of rejection compared with the baseline value (2,817 +/- 801 v 1,943 +/- 255 U/mL). By contrast, the urinary excretion rate, expressed as units of sIL-2R per milligram creatinine, was 26.2 +/- 6.4 compared with 14.2 +/- 2.5 (P < 0.05). Furthermore, when urinary sIL-2R was expressed as a fractional excretion (FE), both the absolute measurement (4.4% +/- 1.7%) and the percent increase (+245%) at the time of rejection provided the greatest degree of discrimination of rejection from those values during allograft stability (1.2% +/- .2% and +2.5%, respectively; P < 0.005). We conclude that (1) serum and urine sIL-2R concentrations are affected by a number of factors during rejection; (2) FE calculations of sIL-2R improve discrimination of rejection from graft stability; and (3) serial measurement of sIL-2R excretion may be a useful adjunct to the diagnosis of rejection and, possibly, the subsequent assessment of response to immunotherapy.