In vitro interactions of thymocytes and thymocyte hybridomas with cortical (R-TNC.1) and medullary (TE-R 2.5) rat thymic epithelial-cell (TEC) lines were studied. It was found that the cortical line had better adhesion capability. It bound exclusively immature CD4+CD8+<mml:math id="E1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>α</mml:mi><mml:mi>β</mml:mi></mml:mrow></mml:math>TCR10 thymocytes, induced apoptosis of a subset of these cells, and stimulhted proliferation of the BWRT (CD4-CD8-<mml:math id="E2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>α</mml:mi><mml:mi>β</mml:mi></mml:mrow></mml:math>TCR-) hybridoma. The medullary line bound both immature and mature thymocytes, decreased their apoptosis, and induced apoptosis of the BWRT 8 (CD4+CD810<mml:math id="E3" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>α</mml:mi><mml:mi>β</mml:mi></mml:mrow></mml:math>TCRhi) hybridoma. Thymocyte differently modulated cytokine production by TEC lines, upregulating the secretion of IL-1 by R-TNC.1 and IL-6 by TE-R 2.5 cells. Finally, coculture of thymocytes with TEC lines resulted in different patterns of protein-tyrosine phosphorylation in thymocytes. These results show the existence of mutual bidirectional interactions between thymocytes and TEC lines in vitro, but these processes differed depending on phenotypic characteristics and origin of TEC lines used.

Miodrag Colic

Dragana Vucevic

Petar Popovic

Aleksandar Dujic

Bidirectional Interactions Between Thymocytes and Thymic Epithelial Cell Lines in Vitro

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

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

The mouse IgG1 monoclonal antibody (mAb) K21 recognizes a 230-kD molecule (K21-Ag) on Hassall&#39;s corpuscles in the human thymus. This mAb also stains cultured thymic epithelial cells as well as other epithelial cell lines, revealing a predominant intracellular localization. Further analysis with mAb K21 on other lymphoid tissues showed that it also stains cells within the germinal centers of human tonsils, both lymphoid (B) cells and some with the appearance of follicular dendritic cells. Double immunostaining of tonsil sections shows that K21-Ag is not expressed by T cells, whereas staining with anti-CD22 and -CD23 mAb revealed some doublepositive cells. A subpopulation of the lymphoid cells express the K21-Ag much more strongly. This K21++/CD23++ subpopulation of cells is localized in the apical light zone of germinal centers, suggesting that K21-Ag may be an important marker for the selected centrocytes within germinal centers and may play a role in B-cell selection and/or development of B-cell memory. Flow cytometric analysis showed that K21-Ag is expressed on the surface of a very low percentage of thymocytes, tonsillar lymphocytes, and peripheral blood mononuclear cells. Analysis of purified/separated tonsillar T and B lymphocytes showed that T cells do not express the K21-Ag; in contrast, B cells express low levels of the K21-Ag, and this together with CD23 is upregulated after mitogenic stimulation. Our data therefore raise the possibility that the K2l- Ag may play a role in B-lymphocyte activation/selection.

Nesrina  Imami

Heather M. Ladyman

Bjarne  Vincents

Abdulhamid  Al-Tubuly

Jona  Freysd&#243;ttir

Moditi L. Sedibane

David A. Taylor-Fishwick

Brian M.J. Foxwell

Mary A. Ritter

K21-Antigen: A Molecule Shared by the Microenvironments of the Human Thymus and Germinal Centers

Klaus  Eichmann

The Lck Paradox: Because of Inconsistent Experimental Evidence, the Role of the Protein Tyrosine Kinase <svg style="vertical-align:-3.27599pt" height="24.125" version="1.1" viewBox="0 0 31.7125 24.125" width="31.7125" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,19.988)"><path id="x70" d="M169 380l92 53q26 16 49 16q80 0 128.5 -56t48.5 -133q0 -108 -72.5 -180.5t-176.5 -91.5q-38 1 -69 18v-131q0 -57 13 -70t71 -18v-27h-236v27q49 5 61 17t12 61v452q0 48 -9.5 58.5t-56.5 16.5v24q66 11 145 43v-79zM169 346v-270q37 -39 94 -39q63 0 101.5 50&#xA;t38.5 134q0 78 -38.5 123t-95.5 45q-45 0 -100 -43z" /></g><g transform="matrix(.012,-0,0,-.012,8.975,11.825)"><path id="x35" d="M153 550l-26 -186q79 31 111 31q90 0 141.5 -51t51.5 -119q0 -93 -89 -166q-85 -69 -173 -71q-32 0 -61.5 11.5t-41.5 23.5q-18 17 -17 34q2 16 22 33q14 9 26 -1q61 -50 124 -50q60 0 93 43.5t33 104.5q0 69 -41.5 110t-121.5 41q-53 0 -102 -20l38 305h286l6 -8&#xA;l-26 -65h-233z" /></g><g transform="matrix(.012,-0,0,-.012,14.686,11.825)"><path id="x36" d="M137 343l67 33q37 17 63 17q79 0 129.5 -53t50.5 -131q0 -92 -58 -156.5t-147 -64.5t-147 68t-58 182q0 63 17 119t43 95.5t61.5 72t69 52t67.5 31.5q62 22 128 33l6 -32q-56 -11 -108 -35q-149 -71 -184 -231zM227 337q-47 0 -95 -27q-6 -23 -6 -70q0 -93 36 -155.5&#xA;t96 -62.5q53 0 78 45.5t25 105.5q0 68 -35 116t-99 48z" /></g><g transform="matrix(.008,-0,0,-.008,20.388,6.113)"><path id="x1D459" d="M238 681l-124 -585q-7 -31 4 -31q10 0 37.5 18.5t49.5 41.5l16 -22q-40 -48 -89.5 -81.5t-76.5 -33.5q-42 0 -16 122l105 488q7 32 0 41t-39 9h-35l5 26q35 3 71 13t58 17.5t26 7.5q14 0 8 -31z" /></g><g transform="matrix(.008,-0,0,-.008,22.674,6.113)"><path id="x1D450" d="M383 397q0 -32 -35 -49q-12 -6 -23 8q-37 45 -84 45t-90 -71q-40 -65 -40 -167q0 -57 22 -86t59 -29q38 0 81.5 24.5t69.5 51.5l16 -21q-44 -53 -104 -84t-109 -31q-56 0 -89.5 41t-33.5 117q0 61 30 124t79 105q33 28 81 50.5t86 22.5q34 0 59 -15.5t25 -35.5z" /></g><g transform="matrix(.008,-0,0,-.008,26.124,6.113)"><path id="x1D458" d="M480 416q0 -21 -18 -41q-9 -11 -17 -7q-20 9 -42 9q-62 0 -140 -78q23 -69 88 -192q17 -31 27 -42t20 -11q16 0 62 46l17 -20q-64 -92 -119 -92q-35 0 -70 66q-41 73 -84 187q-36 -30 -62 -61q-27 -115 -35 -172q-41 -8 -78 -20l-6 6l140 612q7 28 0.5 34t-37.5 7l-34 1&#xA;l5 26q38 4 74 13.5t57 17t25 7.5q12 0 4 -32l-104 -443h2q35 38 97 93q39 35 65.5 56t62 41.5t58.5 20.5q19 0 30.5 -10t11.5 -22z" /></g></svg> in Early Thymic Development Remains Poorly Defined

Autoimmune phenomena are more frequent in thymic epithelial tumors (TET) than in any other human tumor. Mysthenia gravis (MG) is by far the most common autoimmune disease in thymoma patients. MG is characterized by muscle weakness due to autoantibodies against the acetylcholine receptor (AChR), and CD4 +AChR-specific T cells play a pivotal role for the production of these autoantibodies. About 10% of MG patients have a thymoma and, interestingly, only such thymomas exhibit an MG association that maintains thymuslike
morphological and functional features with respect to the homing and differentiation of immature T cells. Since AChR protein is not expressed in thymomas, the specificity of the autoimmunity in thymoma-associated MG is thought to be determined by nonreceptor proteins with AChR epitopes. Such proteins are overexpressed in cortical-type MG-associated thymomas, and medullary thymomas express these proteins at barely detectable levels. Aside from this quantitative difference, the pathogenesis of anti-AChR autoimmunity might be qualitatively
different in these thymoma subtypes. Our findings suggest that an antigen-specific abnormal Tcell selection by cortical-type TET may contribute to the pathogenesis of paraneoplastic MG. In contrast, an abnormal (intratumorous) activation of autoreactive T cells may be operative in medullary thymomas.

Alexander Marx

Anja Schultz

Annette Wilisch

Markus Helmreich

Regina Nenninger

Hans Konrad Müller-Hermelink

Paraneoplastic Autoimmunity in Thymus Tumors

On the basis of both the interleukin-2-receptor (IL-2R) &#945;-chain expression on 16-day-old fetal rat thymocytes and the occurrence of interleukin-2 (IL-2) mRNA-containing cells early during rat thymus ontogeny, we have investigated the possible role of IL-2/IL-2R complex in rat T-cell maturation. For this purpose, we analyzed the effects of the addition of either recombinant rat IL- 2 or anti-CD25 (OX-39)-blocking monoclonal antibodies to fetal thymus organ cultures (FTOC), established from 16-day-old rat embryos. IL-2 stimulated the growth of thymocytes and, as a result, induced T-cell differentiation, whereas OX-39 mAb blocked the maturation of thymic-cell progenitors. Accordingly, these results support the involvement of IL-2/IL-2R complex in rat Tcelldevelopment.

Alberto  Varas

Teresa  Romo

Eva  Jim&#233;nez

Luis  Alonso

Angeles  Vicente

Agust&#237;n G. Zapata

The IL-2/IL-2-Receptor Complex in the Maturation of Rat T-Cell Progenitors

Human immunodeficiency virus (HIV) infections have been characterized by both polyclonal Bcell activation and enhanced responsiveness to B-cell growth factors on one hand and the loss of specific antibody (Ab) responses and refractoriness to the normal signals for B-cell activation on the other. Histopathological studies of lymph node from HIV- and simian immunodeficiency virus (SIV)-infected individuals have indicated initial follicular hyperplasia and the appearance of large irregular germinal centers that undergo progressive involution concomitant with follicular dendritic-cell (FDC) disruption. During this process, follicular dendritic-cell -enriched
lymph-node-cell cultures exhibit increased ability to induce cluster formation (“in vitro germinal centers”), lymphocyte proliferation and antibody production compared to uninfected controls. This paper discusses how enhanced FDC-B-cell interaction within SIV-infected germinal centers may result in a reduced ability to select high-affinity B cells and alter the dynamics of antibodyproducing- cell and memory-cell generation resulting in the observed hyperactivity.

Yvonne J. Rosenberg

Mark. G. Lewis

Marie H. Kosco-Vilbois

Enhanced Follicular Dendritic Cell-B Cell Interaction in HIV and SIV Infections and its Potential Role in Polyclonal B Cell Activation

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