CONTENTS
Review
- Cytokine Signaling/Transcription Factor Cross-Talk in T Cell Activation and Th1-Th2 Differentiation
Ana C. Liberman, Damian Refojo and Eduardo Arzt (Laboratory of Physiology and Molecular Biology, Department of Physiology and Cellular and Molecular Biology, Buenos Aires University, Buenos Aires, Argentina)Abstract. The secretion of interleukin (IL)-2 is a key event in T cell activation. IL-2 allows T cells to enter into the S phase of the cell cycle and divide. After the activation phase takes place, T lymphocytes proliferate and differentiate to generate effector T cells. Thereby, T helper (Th) precursor cells, which are functionally immature, may become Th1 or Th2 effector cells. These subsets are responsible for cell-mediated immunity and humoral responses, respectively. Both, T cell activation and Th differentiation are processes that depend on changes in the pattern of gene expression. The expression and changes in the genes responsible for these events are regulated by transcription factors. This review will focus on both transcription factors involved in the control of IL-2, as well as those that are key in T helper differentiation.
Keywords: T cell differentiation; T cell activation; TCR; IL-2; GATA-3; T-bet.
- Viral Strategies in Modulation of NF-kB Activity
Katarzyna Lisowska and Jacek M.Witkowski (Department of Pathophysiology, Medical University of Gdańsk, Poland)Abstract. Activation of nuclear factor (NF)-kB transcription factors family in response to different stimuli such as inflammatory cytokines, stress inducers or pathogens’ products results in host innate and adaptive immunity. NF-kB plays a central role in promoting the expression of genes involved in inflammatory, immune and apoptotic processes, including those encoding cytokines, chemokines, cytokine receptors or proteins involved in antigen presentation. Although the main function of NF-kB is to activate specific genes in the cells of the immune system, its role in controlling the host cell cycle makes NF-kB an interesting target for pathogenic viruses. Some viruses take advantage of anti-apoptotic properties of NF-kB to escape host defence mechanisms, other use apoptosis to spread. This review describes the role of NF-kB family in immune responses, mechanism of NF-kB activation and different strategies that viruses have developed to modulate NFkB pathway in order to facilitate and enhance viral replication and avoid host immune responses.
Keywords: NF-kB, IKK complex, viral infection, apoptosis.
- The Immunological Synapse
Thomas Klemmensen, Lars Ostergaard Pedersen (Department of Molecular Pharmacology, Lundbeck A/S) and Carsten Geisler (Institute of Medical Microbiology and Immunology, University of Copenhagen, The Panum Institute, Blegdamsvej 3, DK-2200 Copenhagen, Denmark)Abstract. Induction of a proper adaptive immune response is dependent on correct transfer of informations between antigen-presenting cells (APCs) and antigen specific T cells. Defects in information transfer may result in development of diseases, e.g. immunodeficiencies and autoimmunity. A distinct 3-dimensional supramolecular structure at the T cell/APC interface has been suggested to be involved in the information transfer. Due to its functional analogy to the neuronal synapse, the structure was termed the “immunological synapse” (IS). Here, we review molecular aspects concerning IS formation, appearance, and cessation. In addition, proposed functions of the IS are discussed. The process of IS formation occur in a sequential manner initially causing a remarkable large-scale redistribution of a number of integral membrane- and cytosolic proteins. At the T cell/APC interface the structure comprises in its nascent stage a non-random pattern of protein distribution. The protein pattern is regulated during development of the mature IS and is finally organized into concentric rings of co-receptors and adhesive molecules surrounding the T cell antigen receptor (TCR). The relocations of proteins are influenced by passive as well as active mechanisms. Considering the IS as a device enabling cell-cell communication, clarification of its exact function is of huge general as well as therapeutic interest.
Keywords: immunological synapse, signaling, T cell, TCR, MHC.
- Dynamic Control of B Lymphocyte Development in the Bursa of Fabricius
Phillip E. Funk and Jessica L. Palmer (Department of Biological Sciences, DePaul University, Chicago, IL 60614, USA)Abstract. The chicken is a foundational model for immunology research and continues to be a valuable animal for insights into immune function. In particular, the bursa of Fabricius can provide a useful experimental model of the development of B lymphocytes. Furthermore, an understanding of avian immunity has direct practical application since chickens are a vital food source. Recent work has revealed some of the molecular interactions necessary to allow proper repertoire diversification in the bursa while enforcing quality control of the lymphocytes produced, ensuring that functional cells without self-reactive Ig receptors populate the peripheral immune organs. Our laboratory has focused on the function of chB6, a novel molecule capable of inducing rapid apoptosis in bursal B cells. Our recent work on chB6 will be presented and placed in the context of other recent studies of B cell development in the bursa.
Keywords: bursa of Fabricius, B lymphocytes, apoptosis, intracellular signaling.
- New Insights into the Pathophysiology and in Vivo Function of IgG Fc Receptors through Gene Deletion Studies
Ulrich Baumann, Reinhold E. Schmidt and J. Engelbert Gessner (Department of Clinical Immunology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hanover, Germany)Abstract. Fc-receptors for IgG (FcgRs) are critically involved at multiple stages of an immune response, ranging from antigen presentation and regulation of antibody production to the end-stage effector mechanisms of inflammation. Immunolglobulin G autoantibodies that are detectable in the majority of autoimmune diseases are ligands for FcgRs. The three classes, FcgRI, FcgRII, and FcgRIII, vary in their antibody affinity, cellular expression and in vivo function. We review the current knowledge on regulation and diverse functions of the distinct FcgRs and describe the evidence of their important immunoregulatory roles in autoimmunity based on recent work in animal models.
Keywords: IgG Fc receptors, gene deletion, autoimmunity.
- Development and Selection of T Cells: How Many Subsets? How Many Rules?
Paweł Kisielow (Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland)Abstract. Since the discovery indicating that thymus derived lymphocytes (T cells) can be divided into two subpopulations: CD8+ (killer) and CD4+ (helper) cells, subsequent studies revealed bewildering heterogeneity of T cells. In the present review an attempt is made to present the actual picture of T cell heterogeneity, introduce some order into nomenclature and summarize the rules behind the development and selection of different, currently recognized T cell subsets.
Keywords: thymus, T cell development, T cell heterogeneity, positive selection, negative selection, T cell subsets.
Experimental and Clinical Immunology
- Efficacy of Procalcitonin Measurement in Patients after Total Thyroidectomy Due to Medullary Thyroid Carcinoma
Paweł Bolko, Ewa Manuszewska-Jopek, Krzysztof Michałek, Ryszard Waśko, Magdalena Jaskuła and Jerzy Sowiński (Department of Endocrinology, Metabolism and Internal Diseases, Karol Marcinkowski University of Medical Sciences, Poznań, Poland)Abstract. Procalcitonin (PCT) is a protein synthesised by the thyroid C-cells, inside which is cut into calcitonin (CT) and catacalcin. It remains undetectable in serum in normal conditions. Its level increases during inflammation and in small-cell lung cancer. There have been studies suggesting that the PCT level increases in medullary thyroid carcinoma (MTC). So far there have been no reports that would assess the usefulness of PCT detection in MTC. Our aim was to evaluate the usefulness of serum PCT assays in the patients with MTC. We investigated 24 patients at the age of 17-78 years, all after a total thyroidectomy due to MTC. All patients had serum CT concentrations measured with the radioimmune assay (RIA-DPC). The upper limit of CT level was 60 pg/ml. The serum PCT was evaluated with immunochromatographic kit . The reaction was considered positive when PCT level exceeded 0.5 ng/ml. In all cases the C-reactive protein serum level was measured. The statistical analysis was performed with the Statistica 5.1G. The CT levels in all patients varied from 0 to 1410, mean 603.8 pg/ml. In 8 patients the CT level was within normal range, in 6 patients it was marginally and in 10 patients markedly elevated. The PCT test was considered positive in 16 patients. There was correlation between serum PCT and CT concentrations (Spearman test, p<0.0001). The PCT levels varied considerably between patients with normal, marginally and markedly elevated CT levels (Kruskal-Wallis test, p=0.0013). All patients had normal CRP values. Fisher’s exact test revealed a correlation between serum PCT and CT increase (p=0.04). Further studies of a bigger group of patients should be considered, so far, the PCT assay can be thought useful in cases of unclear CT concentration.
Keywords: medullary thyroid carcinoma, procalcitonin, calcitonin, follow-up.
- CD80 and CD86 Expression on LPS-Stimulated Monocytes and Effect of CD80 and CD86 Blockade on IL-4 and IFN-g Production in Nonatopic Bronchial Asthma
Ryszard Rutkowski1, Tadeusz Moniuszko2, Anna Stasiak-Barmuta1, Bożena Kosztyła-Hojna3, Marek Alifier4, Krzysztof Rutkowski5 and Anetta Tatarczuk-Krawiel6 (1Department of Pediatric Allergology, 2Department of Allergology and Internal Medicine, 3Department of Otolaryngology, 4Department of Neonatology Medical University, 5Student of Medical University, 6GlaxoSmithKline, Białystok, Poland)
Abstract. CD80 and CD86 seem to play an important role in the allergen induced secretion of IL-5 and IL-13. Up till now, the expression of CD80 (B7.1) and CD86 (B7.2) on monocytes and kinetics of these molecules expression on lipopolysaccharide–stimulated monocytes in nonatopic asthma have not been defined. Using monoclonal antibodies we have compared the expression of CD80 (B7.1) and CD86 (B7.2) on monocytes of healthy persons and nonatopic asthmatic patients. We have also assessed the effect of CD80 and CD86 inactivation on interleukin (IL)-4 and interferon gamma (IFN-g production in nonatopic asthmatics and healthy subjects. We found that low expression of CD80 on studied monocytes (1.64±0.65 vs. 3.53±1.43%) and moderate expression of CD86 (41.25±134 vs. 49.46±11.49%) were characteristic for asthma. In nonatopic asthma patients inactivation of CD80 or CD86 blockade significantly reduced IFN-g production by T lymphocytes (p<0.02; p<0.03). In both studied groups anti-CD80 antibodies did not diminish T lymphocytes` production of IL-4. However anti-CD86 antibodies significantly (p<0.04) reduced the IL-4 concentration in culture supernatants. Our results confirm that both CD80 and CD86 molecules play on important role in the maintenance and amplification of inflammatory process. It suggests that in the inflammatory process that occurs in the nonatopic bronchial asthma Th1 as well as Th2 lymphocytes are equally important
Keywords: CD80 (B7.1), CD86 (B7.2), IL-4, IFN-g, monocytes, lymphocytes, nonatopic bronchial asthma.