CONTENTS
Mini-Review
- T Cell Immunobiology of Alloimmune Thrombocytopenias
JACK GORSKI, MARYAM YASSAI, SHENHONG WU and KRYSTYNA MAŚLANKAAbstract. Allorecognition and generation of alloantisera depend on T cell help. Here we summarize our recent work on identyfying the T cells that recognize a specific platelet alloantigen generated by a Pro to Leu polymorphism in b -chain of the platelet integrin a Iibb 3. The ability to generate alloantibodies is restricted by HLA-DRB3*0101. By measuring peptide binding to HLA-DRB3*0101, we have shown that the polymorphism controls the generation of the T cell epitope. This is not a result of the polymorphism changing a T cell contact residue, but rather by its generating a peptide anchor. The result is a directional antibody response in which only the b -chain that is antigenic is the one that produces a peptide that binds to the HLA-DR. This mechanism of generating alloantibodies may be a paradigm for a whole class of responses.
Keywords: MHC restriction; peptide binding; alloantibodies.
- Onset and Persistence of the Allergic Inflammation: a Molecular Explanation ?
FABRIZIO SPINOZZIAbstract. Allergic respiratory inflammation in target organs does not occur in any atopic (getically susceptible) subject, since other not fully chracterized factors can influence the subsequent development of overt clinical disease. Here are presented some recent developments in experimental animal and human research that can offer a new “non-classical” interpretation about the way by which allergens are recognized and allergic inflammation persists. These aspects of the immunopathogenesisof allergic diseases can now be viewed as organ-specific pathways, acting independently from other peropheral lymphoid organs. This is a consequence of new knowledge about the function of, and molecular interactions by, intraepithelial gd T cells and CD1+ dendritic cells. The allergic subject, unlike the normal one, is equipped at the mucosal surface by particular T cell and antigen-presenting cell (APC) subsets that enable them to recognize undernatured proteic and non-proteic (glycolipidic) external structures of aerodispersed particles, presented in the context ofCD1 molecules. Once initiated, the mucosal allergic reaction cannot be turned off in atopic individuals because CD4+ allergen-specific T cells lack surface Fas receptor. This defect, yhat impairs the socalled activation-induced programmed cell death (detrmined by Fas/FasL inetraction), is caused by the local Th2-type cytokine milieu.
Keywords: T cells; allergic inflammation; programmed cell death.
- MHC Class II and Negative Regulators of Hematopoiesis
H. JOACHIM DEEG and VLADIMIR LESNIKOVAbstract. HLA-DR antigens a side from their antigen-presenting function have recently been shown to allow for transmembrane signaling. Findings in several model suggest that such a signaling function may occur in hematpoietic tissues. Signals generated via HLA-DR result in upregulation of tumor necrosis factor a (TNF-a ) and nitric oxide as well as an enhanced expression of Fas and its natural ligand (Fas-L), all molecules associated with programmed cell death (apoptosis). While a role of HLA-DR in hematopietic failure remains hypothetical, the data presented into a model of hematopoietic failure initiated by HLA-DR mediated signals.
Keywords: HLA-DR; hematopoiesis; tumor necrosis factor a ; Fas; nitric oxide.
Experimental Oncology
- Therapeutic potential of Biological Response Modifiers Against Transplantable Mouse Tumors of Spontaneous Origin. II. Local Interleukin 2 Treatment of Tumors of Different Immunogenic Strength
ŁUCJA FISZER-MALISZEWSKA, WILLEM DEN OTTER, JANUSZ A. MADEJ and MARIAN MORDARSKIAbstract. This report describes tumor susceptibility to inetrleukin 2 (IL-2) therapy in ralation to tumor immunogenicity. The following lines recently established from spontaneous tumors were used: X5,X6, and X9 mammary tumors of DBA/2, BALB/c and CBA origin, respectively, X7 cacinoma of BALB/c and X18 papilloma of CBA mice. Two spontaneous tumors of long transplantation history, SL2 lymphoma (SL2) of DBA/2 and M109 Madison lung carcinoma (M109) of BALB/c origin, were used as control system. Mice were transplanted with different inocula of tumor cells at day O; IL-2 treatment was initiated on day 1 – 3 or 10 and consisted of daily injections of 5000 or 20 000 IU/mouse given 5 times a week for 3 weeks. SL2 (i.p. – 2 ´ 104 cells) treatment cosisted of i.p. injestions of 5000 or 20 000 IU IL-2 given on days 10 – 14. IL-2 therapy of SL2 bearing DBA/2JIco mice resulted in the significant proportion of cures; however, no response to IL-2 treatment was achieved in SL2 bearing DBA/2Crliw mice. BALB/c mice with the i.p. transplant of M109 responded to IL-2 treatment with 40% inrease in lifespan.. The low-dose IL-2 therapy of the 5 recently established tumors resulted, in general, in transient growth inhibition of the i.m. transplants of line X5, X6, and X7 provided IL-2 was administerde locally. The therapeutic effect depended on the numberof transplanted tumor cells, and the best results begin achieved at cell numbers close to the dose inducing tumor growth in 50% of animals (TD50). We found that the tumors responding to IL-2 treatment were all slowly growing and immunogenic (X6 and X7) or might have viral association (X5) and as such might express foregin antigens.
Keywords: biological response modifiers; interleukin 2; spontaneous mouse tumors; tumor immunogenecity.
- 5-Aminolevulinic Acid Photodynamic Therapy of Transplantable Colon Adenocarcinoma in BALB/c Mice
PIOTR ZIÓŁKOWSKI, KRZYSZTOF SYMONOWICZ, BEATA J. OSIECKA and JERZY RABCZYŃSKIAbstract. We present results of preliminary studies on 5-aminolevulinic acid (5-ALA)-photodynamic therapy (PDT). In order to assess the effectiveness of 5-ALA-PDT we have used BALB/c mice transplnted subcutaneously with mouse colon adenocarcinoma C51. 5-ALA in the dose of 50 mg/kg was given intraperitoneally and 5 h later tumors were exposed to light at total doses from 50 to 75 J/cm2 , wavelength 630 ± 20 nm and light intensity 200 mW/cm2. Several time points following 5-ALA injections have been used to measure protoporphyrin IX (PpIX) concentration in different tissues from unirradiated mice. PDT effects were evaluated with regard to survival time, tumor response and necrosis depth. The main finding in our tumor model was that the optimum tumor to skin ratio of PpIX occurs within 5 h after sensitizer injection. 5-ALA-PDT resulted in prolongation of survival time of treated mice as compared to control animals and, in some cases, in complete response of tumors. PDT also caused increase in tumor necrosis, while no skin photodamage was observed.
Keywords: photodynamic therapy; 5-aminolevulinic acid; colon adenocarcinoma; protoporphyrin IX concentration.
Clinical Immunology
- Interleukin 6 and Its Soluble Receptor in Periodontitis
MAŁGORZATA PIETRUSKA, JAN K. PIETRUSKI, WANDA STOKOWSKA and EWA JABŁOŃSKAAbstract. The paper presents the evaluation of interleukin 6 (IL-6) and interleukin 6 soluble receptor (sIL-6R) values in the blood serum of patients with various forms of periodontitis (P), as confronted with local state. The study involved a group of 15 patients with P, including 4 patients with rapidly progressive periodontitis (RPP), 10 with adult periodontitis (AP) and 1 with juvenile periodontitis (JP). The concentration of IL-6 and its soluble receptor in blood serum were assessed using the immunoenzymatic ELISA method. The clinical state was estimated with the following periodontal indices: plaque index (PI), oral hygiene index (OHI), sulcus bleeding index (SBI), probing pocket depth and probing attachment loss. The P group showed an insignificant decrease in the IL-6 level in serum and a significant increase in sIL-6R concentration, compared with controls. A correlation was found between the level of IL-6 and PI, OHI and SBI.
Keywords: periodontitis; interleukin 6; soluble interleukin 6 receptor.in 6 receptor.
- Concentrations of Leptin and Neuropeptide Y in Maternal Plasma, Umbilical Cord Blood and in Amniotic Fluid in Pregnant Women with EPH-Gestosis
FRANCISZEK KOKOT, IZABELA ULMAN, ANDRZEJ WIĘCEK, TOMASZ IRZYNIEC and JÓZEF ULMANAbstract. Leptin is presumed to be related to body mass index (BMI) and body fat stores and is involved together with neuropeptid Y (NPY) in the regulation of appetite. As pregnancy is accompanied both by changes of BMI and appetite, performance of studies presented in this paper were fully justified. In 43 healthy pregnant women and in 18 pregnant women with mild or moderate EPH-gestosis, concentrations of leptin and NPY were estimated in maternal venous blood, umbilical cord blood and in amniotic fluid. The control group consisted of 26 healthy nonpregnant women. Healthy nonpregnant women showed a BMI of 23.08 + 0.65 kg/m2 which was significantly lower than in healthy pregnant women (26.9 + 0.4 kg/m2, p < 0.001) and in women with EPH-gestosis (29.7+0.9, p < 0.0001). Also in healthy pregnant women the BMI was significantly lower than in EPH-gestosis subjects (p < 0.001). In healthy nonpregnant women plasma leptin levels were significantly lower than in healthy pregnant and EPH-gestosis women (10.9 + 1.68 vs 14.99 + 1.28 vs 21.89 + 2.58 ng/ml, respectively). In umbilical cord blood plasma leptin levels were significantly lower than in maternal blood only in healthy pregnant women (7.37 + 0.69 vs 14.99 + 1.28 ng/ml) but not in EPH-gestosis subjects (18.06 + 3.38 vs 21.89 + 2.58 ng/rnl). Leptin levels in amniotic fluid were significantly lower than in umbilical cord blood both in healthy pregnant women (2.25 + 0.20 vs 7.37 + 0.69 ng/ml) and EPH-gestosis women (6.58 + 2.62 vs 18.06 + 3.38 ng/ml). In EPH-gestosis women leptin levels were significantly higher than in healthy pregnant women in maternal blood (21.89 + 2.58 vs 14.99 + 1.28 ng/ml), umbilical cord blood (18.06 + 3.38 vs 7.37 + 0.69 ng/ml) and amniotic fluid (6.58 + 2.62 vs 2.25 + 0.2 ng/ml). In both examined pregnant groups plasma NPY levels were nonsignificantly lower in healthy pregnant and EPH-gestosis women (42.28 + 4.09 and 43.68 + 8.45 pg/rnl, respectively) than in nonpregnant women (50.65 + 6.13 pg/ml). In nortnal pregnancy a significantly higher NPY level was found in umbilical cord blood as compared with respective values in EPH-gestosis women (116.28 + 17.0 vs 49.65 + 7.01 pg/ml). Finally in both examined groups of pregnant women the amniotic fluid NPY level was of similar magnitude (13.85 + 1.52 and 13.89 + 2.46 pg/ml in healthy pregnant and EPH-gestosis women respectively). No significant correlation was found between fetal birth weight and cord-serum leptin and NPY levels respectively.
Keywords: : leptin; neuropeptide Y; normal pregnancy; EPH-gestosis; umbilical cord blood; amniotic fluid.mniotic fluid.
- CD3+ T Lymphoeytes and Interieukin 2 in Myelomatous Blood Hyperviscosity Syndrome Treated with Plasmapheresis
LIDIA USNARSKA-ZUBKIEWICZ
Abstract. The study was aimed at testing changes of absolute CD3+ T lymphocyte counts and serum interleukin 2 (IL-2) concentrations in 20 patients suffering from myelomatous and macroglobulinemic hyperviscosity syndrome. Mean values have been calculated from assays made before treatment, immediately after plasmapheresis (PP) and after 1 month of subsequent chemotherapy. Patients showing hyperviscosity displayed initial IL-2 values ranging from 529 to 2722 pg/ml. These levels were significantly (p = 0.001) higher than in healthy subjects, in whom IL-2 was undetectable. Absolute CD3+ counts in patients with hyperviscosity ranged from 600 to 1290 G/1 and were significantly (p = 0.05) lower than in healthy controls with a range of 1110 – 1520 G/1. In 6 patients in coma or precoma serum IL-2 concentrations were insignificantly and absolute CD3+ counts significantly (p = 0.02) lower than in hyperviscosity patients with less severe symptoms. After PP the previously elevated serum IL-2 levels diminished by 20%, but absolute CD3+ counts remained unchanged. After 1 month of chemotherapy IL-2 levels increased again in 15 multiple myeloma (MM) patients, but in all patients with Waldenström’s macroglobulinemia (WM) a further decrease of serum IL-2 level was observed. By that time CD3+ counts increased significantly (p = 0.01) being higher than initial values. Effects of combined myeloma treatment and prognostic value of serum IL-2 level and absolute number of CD3+ etermination are discussed.
Keywords: : CD3+ lymphocytes; interleukin 2; hyperviscosity syndrome; plasmapheresis; multiple myeloma; Waldenström’s macroglobulinemia.inemia.