Interleukin 2 receptor expression in renal biopsies and the diagnosis of acute allograft rejection.

The aim of the study is to test the diagnostic usefulness of assessing interleukin 2 receptor (IL2R) expression in infiltrating lymphocytes in renal biopsies from patients with suspected acute renal allograft rejection and to compare the NIH-CCTT and the Banff 97 systems of classifying the histopathologic changes in acute renal allograft rejection. The expression of interleukin 2 (IL2) and IL2R, as shown immuno-histochemically, is the final step in T cell mediated acute renal allograft rejection. Renal biopsies obtained from 40 patients clinically suspected to have early acute allograft rejection were examined histologically to diagnose acute allograft rejection and classified by the two systems. Frozen sections of the biopsies were stained with specific antibody for the presence of IL2R. 31 of the 40 patients were histologically and clinically confirmed to have acute allograft rejection. There was significant correlation with this diagnosis and the demonstration of IL2R on infiltrating lymphocytes. The CCTT system of grading correlated better with the presence of IL2R and the confirmed diagnosis of acute allograft rejection. The immunohistochemical demonstration of IL2R is a useful adjunct in the evaluation of biopsies suspected to show changes of acute cellular rejection. Since IL2 expression reflects the relative proportion of activated lymphocytes in the cellular infiltrate, it is proposed that the degree of IL2 expression may reflect the response of the use of monoclonal antibodies (Humanised/Chimaerised) as anti rejection therapy.

Valores de referencia del receptor soluble de interleucina-2 en recién nacidos de término / Reference values of soluble interleukin-2 receptor in full term newborns

Se determinó la concentración sérica del receptor soluble de interleucina-2 (RSIL-2) en recién nacidos de término (RNT) sanos. La determinación cuantitativa del RSIL-2 se realizó con técnica de ELISA con equipo de INMUNOTECH. Se estudiaron 31 RNT a las 24 horas de vida. Se obtuvo un valor medio de RSIL-2 de 3.281 pg/ml (ñ 759,5 DS), con una mediana de 3.360 pg/ml (rango 1.470-4.704 pg/ml). Los niveles fueron similares en los RNT nacidos por parto y por cesárea, p = 0,79. Conocer los valores de referencia de RSIL-2 en RNT sanos es de importancia para poder interpretar cuándo están elevados por activación del sistema inmune

Interleukin-2 and interleukin-2 receptors in children with rheumatic carditis

This study aimed to assess the role of interleukin-2 [IL-2] and IL-2 receptors [IL-2R] in the pathogenesis of rheumatic carditis. Three groups of children were studied. Group I included 15 children with active rheumatic carditis; Group II included 15 children with inactive rheumatic carditis and group III was composed of 20 healthy control children. Before phytohemagglutinin [PHA] stimulation, group I showed higher mean values of IL-2 and IL-2R than the other two groups. After stimulation, the control group had significantly higher mean values than both rheumatic groups. The mean percent change of IL-2 receptors was higher in controls compared to active and inactive rheumatic carditis. Thus, under resting conditions, there is increased production of IL-2 and IL-2R in rheumatic carditis. This increase is higher in active than in inactive disease. This underlying immunological abnormalities might lead to activation of helper T cells producing more immune complexes and producing tissue damage

Differences in immunophenotyping of mucosal lymphocytes between ulcerative colitis and Crohn's disease

OBJECTIVES: Immunologic studies have characterized the numbers and types of inflammatory cells in diseased inflammatory bowel disease (IBD) mucosa but have yielded conflicting results regarding intestinal lymphocytes activation in IBD. We investigated the levels of lymphocytes subsets, interleukin-2 receptor, transferrin receptor, and T cell receptors in mainly isolated lamina propria lymphocytes. Including intraepithelial lymphocytes of normal colonic mucosa or IBD (ulcerative colitis and Crohn's disease) mucosa to understand the pathogenesis of IBD. We have results from this study. RESULTS: 1) In comparing ulcerative colitis with control, IL-2R (p < 0.05), TR (p < 0.01), and CD3/HLA-DR (<0.05) showed a significant increase. 2) In comparing Crohn's disease with control, CD3 (P < 0.05), TCR alpha/beta (p < 0.01) and TCR gamma/delta (p < 0.05) showed a significant decrease. 3) In comparing Crohn's disease with ulcerative colitis, CD19 (p < 0.01), TR (p < 0.01), TCR alpha/beta (p < 0.01) and TCR gamma/delta (p < 0.05) showed a significant decrease. CONCLUSION: From these results, there are increased T cell markers, IL-2R, TR, and CD3/HLA-DR in UC, but differently, decreased CD3, TCR alpha/beta and TCR gamma/delta in CD compared with control. In addition, definitive differences in lymphocytes markers, CD19, TR, TCR alpha/beta and TCR gamma/delta, which are higher in UC than in CD, may elucidate the different immunopathogenesis between UC and CD.

Soluble interleukin-2 receptor as a clinical parameter for nasopharyngeal carcinoma.

We evaluated whether the serum soluble interleukin-2 receptor (sIL-2R) may be a parameter to monitor the efficacy of treatment for nasopharyngeal carcinoma (NPC). There were 177 NPC patients and 24 healthy controls. The level of sIL-2R was measured with a sandwich ELISA kit. Higher levels of sIL-2R than for controls were found in NPC patients before treatment and in patients with distant metastasis (p < 0.001). There was, however, no difference in sIL-2R levels between controls and NPC patients after radiotherapy in relapse-free or in primary relapse. The sIL-2R levels in sequential testing revealed good correlation with clinical response. The sIL-2R levels were found to be elevated when distant metastasis was detected. Two patients had elevated sIL-2R level up to 5 months before clinical detection of metastasis. These results indicate that serial measurements of sIL-2R levels are worthwhile for NPC patients in their clinical course. The sIL-2R level proved to be an adjunct clinical parameter to monitor the efficacy of treatment of NPC.

Molecular basis of Trypanosoma cruzi-induced immunosuppression. Altered expression by activated human lymphocytes of molecules which regulate antigen recognition and progression through the cell cycle

The mechanisms by which Trypanosoma cruzi causes dysfunction in normal human lymphocytes was studied by using an in vitro system in which purified parasites and normal peripheral blood mononuclear cells are co-cultured in the presence or absence of mitogens. Our results have shown that T. cruzi impairs the expression of receptors for interleukin-2 (IL-2R) and transferrin, activated lymphocyte membrane molecules which play key roles in controlling progression through the cell cycle. T. cruzi also downregulates the expression of constitutive lymphocyte molecules (e.g., CD4, and CD8) involved in the interactions between antigen-presenting cells and T lymphocytes as well as the expression of T cell receptor (TCR) and CD3 molecules. The latter molecular structures are physically associated and are responsible for signaling and transducing activation events resulting from antigen binding. Stimulated B lymphocytes also display reduced IL-2R expression in the presence of T. cruzi. In contrast, neither the expression of EA-1 molecules by T lymphocytes nor that of CD19 and CD20 molecules by B lymphocytes is affected by this parasite. Thus, the T. cruzi effects are selective, not indiscriminate. The activated T cell populations affected by T. cruzi show concomitant reductions in the levels of expression of IL-2R and CD4, IL-2R and CD8, IL-2R and CD3 or IL-2R and TCR as well as in their capacity to proliferate; 3H-thymidine uptake decreases and there is a massive arrest of cells at the G0/G1a phase of the cell cycle. The immunosuppressive effects of T. cruzi are reproduced by a protein molecule(s) released spontaneously by the parasite termed TIF (for trypanosomal immunosuppressive factor). We report herein that TIF does not compete with IL-2 for binding to IL-2R and that shedding of IL-2R is decreased in the presence of T. cruzi. Moreover, the intracellular level of IL-2R was found to be lower than that found in control cells cultured in the absence of parasites. These results suggest that suppressed IL-2R reflects a modification induced by T. cruzi at a time coinciding with or preceding IL-2R mRNA translation. Studies are underway to identify the earliest process targeted by T. cruzi

Serum interleukin-6 in Kawasaki disease

Kawasaki disease (KD) is an acute febrile illness of infancy and early childhood. In spite of extensive studies, the cause of KD is not known. Interleukin 6 (IL-6) has manyfold biological functions involved in the immune or inflammatory responses of the host to various stimuli. Here the author investigated whether IL-6 might be responsible for manifestations of KD, such as immunoglobulin hypersecretion, lymphocyte activation and systemic vasculitis. Serum IL-6 levels in KD were determined by ELISA. Usually sera from healthy children contained only negligible levels of IL-6. Serum IL-6 was markedly elevated in all patients with acute KD, which gradually decreased during the course of the disease. Serum IL-6 correlated with serum concentration of C-reactive protein and with serum soluble interleukin-2 receptor level, but did not show any correlation with peak platelet count during subacute phase of the disease. Increased serum IL-6 level did not show any relation to development of coronary aneurysms and dilatation. Further studies will be needed to examine the source and the pathogenetic roles of increased serum IL-6 in KD.

Cell changes and soluble interleukin-2 receptors (Tac peptide) in leprosy reversal reactions using suction-induced blisters.

The cellular contents and soluble interleukin-2 receptor (IL-2R) [Tac peptide] of skin blisters induced by suction over 7 reversal reaction (RR) patients were examined using immunoperoxidase and ELISA techniques respectively. The helper T activity (CD4+ cells) and helper:suppressor ratio were significantly greater in borderline lepromatous (BL) lesions with RR than in quiescent BL lesions. Interestingly, the intracutaneous levels of Tac peptide were elevated and directly correlated with the increases in CD4+ cells. The systemic administration of corticosteroids revealed a reduction in the numbers of CD4+ cells in the lesions. These results indicate that RRs are manifestations of a spontaneous increase in delayed type hypersensitivity (DTH) and possibly cell mediated immunity (CMI) in leprosy patients. The mechanism of such changes in immunity is of considerable value in understanding reversal reactions and the underlying determinants of DTH and CMI in leprosy and this in turn will have a bearing on the potential for proposed vaccines or immunotherapy.

Bronchoalveolar T-lymphocytes and subsets in pulmonary tuberculosis and bronchogenic carcinoma.

Analysis of T-lymphocytes and their subsets in the blood and bronchoalveolar lavage fluids from 12 patients with active pulmonary tuberculosis, 12 patients with bronchogenic carcinoma and 11 healthy volunteers was aimed at identifying their immunologic functions and interrelationships. In patients with active pulmonary tuberculosis, there was a significant increased in the percentage of T-cells bearing IL-2 receptor both in the blood and bronchoalveolar lavage fluids, whereas patients with bronchogenic carcinoma exhibited an increase in the suppressor T-cells and T-cells bearing IL-2 receptor in the blood only. The presence of T-cells bearing IL-2 receptor is generally accepted to be the hallmark of recently active specific antigen activation of the helper T-lymphocytes together with monokine IL-1 stimulation. Suppressor T-cells, on the other hand, play a role in the immunopathogenesis of lung cancers and lung metastasis.

Ativaçäo in vivo de linfócitos T em pacientes com esclerose múltipla / In vivo T-lymphocytes activation in patients with multiple sclerosis

Pacientes com esclerose múltipla apresentam flutuaçöes em subtipos de linfócitos no sangue periférico. No presente trabalho, os autores demonstram uma maior incidência de linfócitos ativados em pacientes com atividade clínica ou em surto, detectados através de anticorpos monoclonais contra os receptores de transferrina e inteleucina

Inmunosupresión en lepra / Immunosuppression in leprosy

Son varios los trabajos que tratan de demostrar que en la formal lepromatosa (LL) de la lepra, existirían mecanismos supresores de la respuesta inmune. Al emplear un método de inducción inespecífico, como el sistema de la Concavalina A (ConA), observamos que los pacientes LL tenían disminuida la función supresora, valorada sobre un sistema de proliferación celular T; dicha función tendía a normalizarse durante el episodio de eritema nudoso lepromatoso (ENL). En este sistema demonstramos además, que las células CD8+ (Leu 2a+) eram capaces de interferir en la generación de supresión. Observamos además, que un alto porcentaje de pacientes LL tenían una supresión espontánea elevada; en este tipo de supresión hallados. Por otra parte, hemos demostrado que en este sistema tendría un papel importante el sistema supresor de los monocitos, a través de la liberación de factores solubles (PGE2). Al evaluar la capacidad que tiene el M. leprae para inducir especificamente supresión in vitro la proliferación célular T, hallamos que en los pacientes LL el M. leprae no inducía supresión. Paralelamente, determinamos en sangre periférica, el número de células que tenían el antígeno Leu8+. Observamos que este antígeno estaba marcadamente disminuido, en la fracción de células T, en los pacientes LL y tendía a normalizarse durante el receptores para IL-2 (Tac) durante la etapa de inducción era similar tanto en los TT com LL. La capacidad de las células para proliferar frente a los mitógenos empleados...