The cellular and molecular requirements for β-cell damages in an immune-mediated toxininduced insulin-dependent diabetes mellitus have been studied in the model of multiple low-dose streptozotocin-induced diabetes in rats and mice. It was found that strain-related susceptibility to diabetes induction correlated with a higher level of IL-2, IFN-γ, and TNF-α production, whereas such differences were not observed when IL-1 and NO production by macrophages were analyzed; elimination of immunoregulatory RT6+T cells that increases IFN-γ production, enhances susceptibility to MLD-STZ-induced diabetes; mercury-induced Th-2 cells downregulated
the disease; IFN-γ-mediated macrophage activation to produce proinflammatory cytokines rather than NO is an important event in early diabetogenic effects of invading macrophages; inhibition of IL-1 activity downregulates diabetes induction; and generation of NO in β cells appears to be important for diabetogenic effects. Taken together, data indicate that MLD-STZ diabetes is induced by Th-1 lymphocytes that secrete soluble effector molecules that activate macrophages and promote destruction of β cells possibly by both nitric oxide and nonnitric oxide-mediated mechanisms.

Miodrag L. Lukic

Stanislava Stošic-Grujicic

Allen Shahin

Effector Mechanisms in Low-Dose Streptozotocin-induced Diabetes

Intercellular channels called gap junctions enable multicellular organisms to exchange
information rapidly between cells. Though gap junctions are held to be ubiquitous in solid
tissues, we have only recently found them in the lymphoid organs. Functional direct cell-cell
communication has now been confirmed by us and other groups in bone marrow, thymus, and
in secondary lymphoid tissues. What functions do they serve in the lymphoreticular system
where, so far, only cytokines/growth factors and adhesion molecules have been considered as
regulators? Here we show evidence for and refer to published work about functional direct cellcell
communication through gap junctions in germinal center reactions and make proposals for
their role in the immune response.We found a large amount of the connexin43 (Cx43) gap junctions in the germinal centers of
secondary lymphoid follicles. Ultrastructurally and immunohistologically, most of the junctions
were detected on the processes of follicular dendritic cells (FDC) enveloping nondividing
centrocytes in the light zone of germinal centers where B-cell selection is thought to take place.
Further support for this finding came by revealing the Cx43 mRNA in situ at the same location
as the protein. On antigen challenge, gap junctions appeared on the FDC as they formed
meshworks in germinal centers. In order to find out which germinal center cells communicate
directly, we separated FDC-rich, low-density, B-cell fractions from human tonsil. In culture, we
injected single FDC with the low-molecular-weight fluorescent dye, Lucifer Yellow (Mr 457
Da), which passed between adjacent FDC and sometimes from FDC to B cells.Based on these findings and their assigned functions in other tissues, gap junctions may
contribute to germinal center reactions in the following ways: (1) they may regulate follicle
pattern formation by controlling FDC growth, (2) they may be involved in FDC-B-cell signaling
contributing to the final rescue of selected B cells from apoptosis, and (3) they may enable FDC
to work as a functional syncytium providing a cellular internet for integrating germinal center
events. Data supporting these interpretations are briefly discussed.

Tibor Krenacs

Martin Rosendaal

Gap-Junction Communication Pathways in Germinal Center Reactions

Macrophages are major cellular inhabitants of cycling and pregnant mammalian uteri. Their densities and patterns of tissue distribution in this organ fluctuate in concert with levels of circulating female sex steroid hormones, estrogens and progesterone, and their production of various effector molecules also may be hormonally regulated. Hormonal control may be achieved by direct binding to receptors or by indirect pathways where hormones modulate production of various autocrine and paracrine cytokines and growth factors that then target to
resident macrophages and influence their secretory profiles. In this paper, we marshall evidence supporting the concept that progesterone acts as a powerful negative regulator of these versatile cells, reducing their migration into the uterus and impairing their ability to produce potent effector molecules such as nitric oxide that could interfere with the success of pregnancy.

Joan S. Hunt

Lance Miller

Jeralyn Sue Platt

Hormonal Regulation of Uterine Macrophages

To determine if major thymic neuropeptides and neurotransmitters can directly influence the functional activity of cultured rat thymic epithelium, neuropeptides and neurotransmitters were applied, and intercellular communication, proliferation, and thymulin secretion assessed. After injections of a mixture of lucifer yellow dextran (too large to pass gap junctions) and cascade blue (which does) into single cells, some neuropeptides decrease dye coupling: 0.1 mM GABA (P &lt; 0.0001), 100 nM NPY (P &lt; 0.0001), 100 nM VIP (P &lt; 0.001), 100 nM CGRP (P &lt; 0.001), 100 nM SP (P &lt; 0.01), and 0.1 mM histamine (P &lt; 0.01), whereas 0.1 mM 5-HT, mM acetylcholine, and 1 μM isoproterenol (<mml:math id="E1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>β</mml:mi></mml:math>-adrenergic agonist) had no effect. Proliferation
(incorporation of tritiated thymidine) was increased by CGRP (P = 0.004) and histamine (P &lt; 0.02), but decreased by isoproterenol (P = 0.002), 5-HT (P = 0.003), and acetylcholine (P &lt; 0.05). The percentage of multinucleate cells was decreased after isoproterenol (2.5%), and increased after 5-HT (21.3%), GABA (15%), and histamine (15.1%). Compared to controls, thymulin in the supernatant was decreased after challenge with acetylcholine (52%), isoproterenol (71%), 5-HT (73%), and histamine (84%). This study demonstrates direct effects
of neuropeptides and neurotransmitters on functional aspects of cultured thymic epithelial cells.

Gail M. Head

R. Mentlein

Birte Von Patay

J. E.G. Downing

Marion D. Kendall

Neuropeptides Exert Direct Effects on Rat Thymic Epithelial Cells in Culture

Irmgard FöRster

Controlling Autoreactivity of CD4 T Cells by Local Tolerance Induction

Next to conventional B cells (or B-2 cells), peritoneal B-1 cells have been shown to contribute significantly to the production of IgA-secreting plasma cells in the gut. Evidence for this was mainly based on studies comprising manipulated animals, including lethally X-irradiated and transgenic mice. To examine the ability of peritoneal B-1 cells from untreated mice to switch actively to IgA in vivo, we performed RT-PCR analysis on FACS-sorted peritoneal B-cell subsets from untreated BALB/c mice in order to examine the presence of germline C<mml:math id="E1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>α</mml:mi></mml:math> mRNA and mature C<mml:math id="E2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>α</mml:mi></mml:math> mRNA transcripts. Germline C<mml:math id="E3" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>α</mml:mi></mml:math> and mature C<mml:math id="E4" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>α</mml:mi></mml:math> transcripts were readily
detectable in peritoneal B-1 cells (defined as IgMbright/IgDdull), but not, or very little, in peritoneal B-2 cells (defined as IgMdull/IgDbright). Moreover, by subdividing the B-l-cell population in CD5+ B-1a cells and CD5- B-1b cells, it was shown that in vivo expression of germline C<mml:math id="E5" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>α</mml:mi></mml:math> and mature C<mml:math id="E6" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>α</mml:mi></mml:math> transcripts was largely restricted to the B-1b-cell lineage. These results indicate that peritoneal B-1 cells indeed are capable to switch to IgA under normal physiological conditions and hereby further support the view that B-1 cells contribute significantly to the mucosal IgA response, albeit this function appears to be restricted to the B-1b-cell subset.

Rick De Waard

Peter M. Dammers

James W. Tung

Aaron B. Kantor

Jennifer A. Wilshire

Nicolaas A. Bos

Leonore A. Herzenberg

Frans G. M. Kroese

Presence of Germline and Full-Length IgA RNA Transcripts Among Peritoneal B-1 Cells

P.  Nieuwenhuis

Introduction to the Proceedings of the 12Th Germinal Centre Conference &#8212; Thirty Years of Germinal Centre Conferences

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Journal of Immunology Research provides a platform for scientists and clinicians working in different and diverse areas of immunology and therapy.

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Chief Editor, Professor Holland, has a background focusing on researching the development of conjunctival fibrosis and the characterisation of immune responses to potential C. trachomatis vaccine candidates.

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Journal of Immunology Research - Table of contents 1998

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Journal of Immunology Research provides a platform for scientists and clinicians working in different and diverse areas of immunology and therapy.

Journal of Immunology Research