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G Otten

Publications and source records attributed to G Otten.

At least 19 recordsLinked to original sources

Nakahara memorial lecture. Regulation of T lymphocyte responses: interactions among receptors.

Murine helper T lymphocytes (HTL) have been categorized on the basis of the lymphokines they secrete. TH1 cells produce interleukin 2 (IL-2), interferon-gamma (IFN-gamma), and lymphotoxin, whereas TH2 cells produce IL-4 and IL-5 but not IL-2 or IFN-gamma. Both cell types apparently can produce IL-3, granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor. We have found that there is at least one additional subset which secretes IL-4 and IFN-gamma. These helper T lymphocyte subsets also respond differently to immunoregulatory processes. T cell clones of all subtypes can proliferate in response to exogenous IL-2, but IL-4 apparently induces a proliferative response only in those subsets that produce IL-4. IFN-gamma inhibits the proliferation of TH2 clones, but does not affect the proliferation of TH1 clones, cytolytic T lymphocyte (CTL) clones, or cells that produce both IL-4 and IFN-gamma. TH1 cells pretreated with a saturating concentration of IL-2 do not proliferate when stimulated with anti-CD3 monoclonal antibody (mAb). However, proliferation of TH2 cells is enhanced by IL-2 pretreatment, while the TH1 clones or CTL clones through the T cell receptor (TCR) profoundly inhibits IL-2-induced proliferation of those cells, whereas such stimulation either has very little effect or augments the proliferation of IL-4-producing clones. Collectively, these data suggest that the combined influence of these cytokines and intensity of TCR stimulation may determine which cell types expand in number during a particular immunological situation.

Animals

Interleukin 2 inhibits antigen-stimulated lymphokine synthesis in helper T cells by inhibiting calcium-dependent signalling.

Certain L3T4+, Lyt-2- cloned murine helper T lymphocytes (HTL), when cultured with a high concentration of interleukin 2 (IL 2), become temporarily unresponsive to antigenic stimulation, as indicated by failure to proliferate and by reduced secretion of lymphokines when challenged with antigen. Exposure of cloned HTL to IL 2 also renders these cells less responsive to concanavalin A (Con A). Here we demonstrate that antigen-unresponsive HTL also accumulate reduced levels of lymphokine mRNA, thus indicating a pretranslational block of the response to antigen. However, HTL which had been pretreated with IL 2 and were unresponsive to antigen responded strongly to antigen + A23187 or to A23187 + PMA but failed to respond to antigen + PMA. With HTL made unresponsive to antigen or to Con A by exposure to IL 2, increases in intracellular calcium ion levels stimulated by Con A also were reduced. Thus, for mouse HTL clones, the IL 2-induced state of unresponsiveness to antigen or Con A appears to reflect an inability of such HTL to increase intracellular free calcium to a level sufficient for activation of lymphokine genes.

Animals

PMA alone induces proliferation of some murine T cell clones but not others.

The responses of cloned murine T cell lines to the phorbol ester, phorbol myristate acetate (PMA), were investigated. PMA alone was able to stimulate proliferation of some clones but not others. Two Lyt-2+, cloned cytolytic T lymphocyte (CTL) lines proliferated in response to stimulation by PMA alone, but several L3T4+, cloned helper T lymphocyte (HTL) lines did not. In contrast, all clones tested released lymphokines in response to stimulation by the combination of PMA and the calcium ionophore A23187. Moreover, all clones proliferated in response to stimulation by the combination of PMA and A23187. The proliferation of HTL in response to PMA + A23187 could be completely inhibited either by cyclosporine A (CsA) or by PC61.5, a monoclonal antibody directed against the murine IL 2 receptor; however, the proliferation of CTL in response to PMA alone was not affected either by CsA or by PC61.5. These results suggest that of the murine T cell clones tested, HTL proliferate in response to stimulation via an IL 2-dependent, autocrine pathway; in contrast, CTL, in addition to an IL 2-dependent pathway, may possess an additional IL 2-independent pathway of proliferation. CTL that proliferate in response to stimulation by PMA alone may be useful models in the study of T cell proliferation.

Animals

Cloned helper T lymphocytes exposed to interleukin 2 become unresponsive to antigen and concanavalin A but not to calcium ionophore and phorbol ester.

Two cloned murine helper T lymphocyte (HTL) lines were used to investigate the immunoregulatory properties of highly purified interleukin 2 (IL2). The clone, designated J6.19, secretes lymphokines, including IL2, and proliferates when stimulated with ovalbumin in the presence of I-Ak-bearing spleen cells, while the alloreactive clone, L2, secretes lymphokines, including IL2, and proliferates when stimulated with Mlsa,d-bearing spleen cells. When either clone was exposed to a high concentration of pure IL2 for 1 to 2 days in the absence of either antigen or spleen cells, the HTL became unresponsive to rechallenge with antigen. Unresponsiveness to antigen was indicated by an inability of HTL to proliferate or secrete usual amounts of IL2 or colony-stimulating factor. Within 5-7 days after exposure to IL2, the cloned HTL again responded to antigen. Thus, in addition to being a growth factor for HTL, IL2 can limit the magnitude of the HTL response to antigen. L2 or J6.19 cells could also be induced to secrete lymphokines by the lectin, concanavalin A (Con A) or by a combination of the calcium ionophore, A23187, and phorbol myristate acetate (PMA). After exposure of L2 or J6.19 cells to sufficient IL2 to induce unresponsiveness to antigen, cells were also unresponsive to Con A, as indicated by a reduction in the level of lymphokines secreted. In contrast, lymphokine levels stimulated by A23187/PMA were comparable to those produced by cells not exposed to IL2. The failure of antigen to stimulate lymphokine release and proliferation by HTL previously exposed to IL2 therefore may result from an inability of HTL to recognize antigen or to transduce effectively the antigen recognition signal. Several T cell surface molecules are known to be involved in antigen activation of HTL; these include the antigen receptor and the "associative recognition" structures L3T4 and LFA-1. We observed that L2 cells, rendered unresponsive to antigen by exposure to IL2, expressed normal levels of antigen receptor, as identified by the monoclonal antibody, KJ16-133.18. Furthermore, expression of L3T4 and LFA-1 was not decreased. Unresponsiveness to antigen induced by IL2 thus could not be correlated with decreases in the expression of antigen receptors, L3T4, or LFA-1. Unresponsive HTL may therefore be capable of recognizing antigen but the signal generated by antigen binding may be attenuated during its transduction, resulting in the failure of cloned HTL to proliferate or secrete lymphokines at the usual levels.

Animals

Sympathetic ablation alters lymphocyte membrane properties.

Ablation of the peripheral sympathetic nervous system by treatment of adult (axotomy) and neonatal (sympathectomy) mice with 6-hydroxydopamine hydrobromide produced significant changes in the distribution of cell surface molecules detected on spleen lymphocyte populations. The surface molecules that were studied consisted of the beta-adrenergic receptor and the Thy-1.2 and Lyt-2 surface antigens associated with lymphocyte subpopulations. beta-Adrenergic receptor density, as measured by 3H-dihydroalprenolol binding, was found to be significantly higher on control mouse splenic B cells than on T cells. beta-Adrenergic receptor density was seen to increase in both T and B spleen cell populations after axotomy. The Thy-1.2 and Lyt-2 surface antigens present on cell populations from mouse spleens were labeled using fluorescent monoclonal antibodies and quantitated using a fluorescence-activated cell sorter. A significant increase in the percentage of Thy-1.2 positive cells represented among the total spleen lymphocyte population was detected in axotomized mice. A corresponding increase in the representation of Lyt-2-positive cells, a subset of the Thy-1.2-positive population, was also found. In contrast, while the percentage of Thy-1.2-positive cells per total spleen lymphocyte population were not found to differ between control and sympathectomized mice, a significantly lower percentage of Lyt-2 positive cells within the Thy-1.2-positive population appeared in sympathectomized mice. Suppressor/cytotoxic cell function, as well as properties relating to the recognition of major histocompatibility complex antigens, have been associated with the Lyt-2 antigen. The relative distributions of lymphocyte subpopulations, as indicated by surface markers, and their beta-adrenergic receptors may play an important role in the physiologic functions and interactions between lymphocytes that respond to sympathetic nervous system innervation.

Animals

[Anastomosis prolapse of the gastric mucosa].

X-rays of 91 patients who underwent gastric surgery between 1973 and 1977 were retrospectively evaluated. We found 16 large mucosal prolapses through the gastroduodenal anastomosis and another six with a so-called anastomosis bulge. Of these patients, 77% presented complaints in relation to delayed gastric emptying. When analyzing the prolapse frequency, patient age at the time of surgery, type of surgery, and suture technique, we found that mucosal prolapse occurred mostly in older patients with an extensive gastric resection after oralis-partialis anastomosis and after employing the two-layered suture technique.

Adult

[Emptying of the stomach after selective proximal vagotomy (author's transl)].

Cream cheese containing 14C-labelled glutaminic acid was given to patients after proximal selective vagotomy and 14CO2 measured in the expired air in order to test the gastric emptying process. Results do not allow exact quantitative evaluation, however definite changes of gastric emptying for up to 6 month after surgery could be demonstrated.

Carbon Radioisotopes

[Increased kidney cell proliferation caused by folic acid treatment after dichromate induced renal failure (author's transl)].

Folic acid is given intravenously to rats 5 to 10 days after a dichromate induced damage of the kidneys. These injection cause an additional damage in the function and structure of the kidneys, but on the other hand, they induce a cell proliferation detected by the increased uptake of thymidine. This cell proliferation in the kidney-tissue seems to be a part of specific reactions to the folic acid.

Animals

[Persistent duodenal septum in an adult].

A case of duodenal obstruction by a congenital duodenal web in a 34-year-old woman is presented. A mucosal diaphragm obstructed the duodenum. It showed an excentric opening of 0.8 cm diameter, but the dilated diaphragm caused a total stop during the last months. Despite a typical history, exact X-ray, and endoscopic examination, the correct preoperative diagnosis was not found, because nobody thought it possible, that a mucosal diapharm of the duodenum could persist for 34 years.

Adult