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Y Ron

Publications and source records attributed to Y Ron.

At least 73 records · Page 4Linked to original sources
PubMed1984

Accessory cells and T cell activation. The relationship between two components of macrophage accessory cell function: I-A and IL1.

Accessory cells are required for the activation of helper T cells. We have examined two characteristics of accessory cells, their expression of I-A, and their ability to release IL1. We provide evidence that these two properties are related, and postulate that membrane I-A molecules participate in the pathway leading to IL1-release. Experimental results are described relating I-A to IL1-release as follows: 1. In vitro-educated Ly1 T cells stimulate IL1-release from M phi; this process is H-2-restricted and blocked by anti-I-A antibodies. 2. H-2-restriction between T cells and M phi is overcome in the presence of ConA, but this unrestricted interaction is also blocked by anti-I-A. 3. LPS stimulation of IL1-release is blocked by anti-I-A. These findings suggested an active role for I-A molecules on IL1-producing cells. We next describe a series of experiments designed to assess the requirements for I-A versus IL1 during T cell activation. In a number of experimental systems, T cells demonstrated a requirement for I-A-recognition, but none that could not also be satisfied by IL1: 1. Generation of helper T cells in allogeneic chimeras. 2. Proliferation of KLH-primed lymph node cells. 3. Proliferation of KLH-primed lymph node cells from chronically anti-I-A-suppressed mice. 4. Proliferation of GAT-primed lymph node cells from nonresponder mice. These findings suggest that for many kinds of T cells (not necessarily all) the apparent requirement for I-A-recognition is primarily involved in stimulating IL1-release from accessory cells.

Animals↗
PubMed1984

The effect of febrile temperatures on biologic actions of interferons: abrogation of suppression of delayed-type hypersensitivity and antibody production.

Interferons (IFN) have a complex immunoregulatory effect on all cells of the immune system. In most cases in which IFN had an enhancing effect, the suggested mechanism was inhibition of the generation or activity of suppressor cells. In the present study, we examined the effect of IFN on suppression of the delayed-type hypersensitivity (DTH) response. Suppression was induced with a low antigen dose of sheep erythrocytes (SRBC), and IFN was found to abrogate both the suppressed state and the transferability of this state. Cyclophosphamide had the same effect. However, the in vitro generation of suppressor cells was not altered by the addition of IFN to the culture medium at a normal temperature (37 degrees C). To reconcile the disparity between the successful anti-suppressive action of IFN in vivo compared with its failure in vitro, we considered the possibility that the pyrogenic action of IFN in vivo might create the optimal thermal environment for its anti-suppressive action. Indeed, when IFN was then tested in vitro at a febrile temperature (39.3 degrees C), it completely blocked the generation of suppressor cells. On the other hand, once suppressor cells were generated at 37 degrees C, IFN had no effect on their ability to suppress a fresh culture either at 37 degrees C or at 39.3 degrees C. IFN also had no effect on the generation of helper cells at either temperature, but help was greatly enhanced by high temperature alone. In vivo, we found our IFN preparation to be pyrogenic and observed that an anti-pyretic drug given before and during antigen stimulation abrogated the anti-suppressive effect of IFN. We suggest, therefore, that the febrile state induced by IFN promotes its action on suppressor cells.

Animals↗
PubMed1983

Splenic B cells function as immunogenic antigen-presenting cells for the induction of effector T cells.

Previous studies performed in our laboratory have revealed that an ordered, sequential, tricellular interaction is obligatory for the antigen-driven induction of a specific effector memory T cell. Thus, it was found that antigen-pulsed peritoneal macrophages signal, in spleen cells, the generation of antigen-specific initiator lymphocytes. These lymphocytes, following injection to syngeneic recipients, recruit, in the draining lymph nodes, "virgin" antigen-reactive T lymphocytes. Although the nature of the first and last cell in the interacting sequence was well characterized, the identity of the intermediary initiator splenic cell was obscure. Studies were carried out to characterize the nature of the splenic initiator cells. It was found that spleen cells from nu/nu, adult thymectomized and neonatal thymectomized, or spleen cells from normal donors which had been subjected to cytolysis using anti-Thy-1.2 antibodies in the presence of complement, did generate, following interaction with keyhole limpet hemocyanin (KLH)-fed macrophages, specific initiator cells. Carrageenan impairment of spleen macrophages did not affect the generation of initiator cells, nor did the depletion of dendritic cells from the spleen. On the other hand highly enriched B cell, but not highly enriched T cell populations, when seeded on KLH-pulsed macrophages, generated antigen-specific initiators, which, in vivo, recruited antigen-reactive T cells. It thus appeared that B lymphocytes can function as intermediary obligatory antigen-presenting cells and actively transfer immunogenic signals from peritoneal antigen-presenting cells to T lymphocytes. These findings may therefore suggest that antigen-specific B cells do not function solely as antibody-producing cells, but, once activated by macrophages, may control the induction and differentiation of some antigen-reactive T cell subsets. Thus, one can view the B cell as an important regulatory cell of both cellular and humoral immune functions. The significance of this observation with regard to Ir gene control at the level of B lymphocytes is discussed.

Animals↗
PubMed1983

Defective induction of antigen-reactive proliferating T cells in B cell-deprived mice. II. Anti-mu treatment affects the initiation and recruitment of T cells.

Mice injected from day of birth onwards with rabbit anti-mouse IgM (antim-mu) antibodies were found to be B cell-deficient and defective for the induction of antigen-reactive proliferating T cells (TPRLF). This defective induction was not due to the absence of circulating antigen-specific antibodies since the daily injections of such antibodies during exposure to antigen did not restore the ability of anti-IgM treated animals to generate TPRLF. Analyzing the cellular events implicated in the induction of virgin antigen-reactive T cells, anti-mu-treated mice manifested impairment of the three interacting cell types involved in the induction of TPRLF. Thus, peritoneal and splenic antigen-presenting cells from such animals were impaired in their capacity to signal a primary antigen-specific T cell reaction. Their splenic lymphocytes could not function as initiator cells in transferring immunogenic signals to recruit TPRLF in normal recipients. Potent antigen-specific splenic initiator cells failed to induce the recruitment of specific TPRLF in anti-mu-treated mice. The defective induction of TPRLF in anti-mu-treated mice may be due to a functional impairment of cells expressing membrane-bound IgM molecules which seemingly play a central role in the transfer of immunogenic signals for the recruitment of antigen-specific circulating T cells. We suggest that splenic B cells function as initiators in the transfer of antigen-induced signals from peritoneal antigen-presenting cells to T cells. These seems to be the primary targets of anti-mu treatment.

Animals↗
PubMed1983

Defective elicitation of delayed-type hypersensitivity in W/Wv and SI/SId mast cell-deficient mice.

Previous studies have indicated that cutaneous mast cells are involved in the elicitation of delayed-type hypersensitivity (DTH) in mice. Mast cells are thought to be required in DTH to release serotonin to open gaps between endothelial cells, allowing entrance of effector cells into the tissue. Two different strains of mice with independent genetic defects that lead to a substantial mast cell deficiency (W/Wv and SI/SId), and their normal littermate +/+ controls, were studied for their ability to express DTH. Both strains were shown to be deficient in serotonin-containing mast cells at skin sites of preferential elicitation of DTH in normal mice, such as the ear or footpad. Defective DTH was found in both mast cell-deficient strains by using two different systems: 1) sheep erythrocyte-induced footpad DTH, and 2) picryl chloride-induced contact sensitivity ear swelling responses. Adoptive transfer experiments demonstrated that abnormal DTH in mast cell-deficient mice was due to a defect in the elicitation of DTH, rather than a defect in the induction of effector T cells. In these experiments, the ability to elicit DTH could be transferred to normal +/+ mice with sensitized cells from mast cell-deficient mice, but sensitized cells from +/+ mice could not transfer DTH responsiveness to mast cell-deficient mice. In addition, no defects in numbers of epidermal Langerhans cells or in antigen-presenting cell function were found in W/Wv or SI/SId mice. We therefore concluded that abnormal elicitation of DTH in W/Wv and SI/SId mice was probably due to their mast cell deficiency. The inability of mast cell-deficient mice to express DTH was overcome when sensitized T cells and specific antigen were placed in the extravascular tissues by local passive transfer. These results suggest that mast cell release of vasoactive mediators, such as serotonin, is required in DTH to allow effector T cells to leave the intravascular space, enter the tissues, and become activated by antigen to release chemoattractant lymphokines that recruit a nonspecific infiltrate of inflammatory cells.

Animals↗
PubMed1982

Mechanisms controlling differentiation and function of antigen-presenting macrophages.

We have briefly reviewed our studies on the mechanisms controlling the differentiation and activation of peritoneal antigen-presenting cells. We demonstrated that the peritoneal population is composed of two main subsets of cells, only one of which participates actively in primary antigen presentation. The latter is missing in athymic mice and seems to differentiate under the influence of the shortlived, cortisone-resistant subpopulation of thymocytes. The maturation of the peritoneal macrophages is subjected also to an additional inducing effect, that of the spleen. Macrophages from splenectomized donors are impaired both with respect to antigen presentation to naive and to primed lymphocytes, and with respect to phagocytosis of "opsonized" bacteria. The mature antigen-presenting cell is subjected to activating signals deriving from the Fc-bound Ig molecule. This is mediated via a tetrapeptide, tuftsin, which is cleaved off the CH2 portion of the Ig and activates the immunogenic effect of the antigen-pulsed macrophage.

Animals↗
PubMed1982

Effect of splenectomy on the progression of postoperative pulmonary metastases of the 3LL tumor.

Surgical excision of the local intrafootpad tumor of the 3LL lung carcinoma is followed by accelerated growth of its lung metastases. When, however, splenectomy was performed concomitantly with tumor excision, the acceleration of lung metastases was prevented. In cases where excision of the local tumor took place when it reached large sizes, concomitant splenectomy did not prevent the accelerated growth of the lung metastases. If, however, at these stages of tumor growth splenectomy was performed 3 days prior to the excision of the tumor, it did prevent the accelerated growth of metastases. Intrafootpad reinoculation of tumor cells following tumor excision and splenectomy caused further reduction in metastatic growth. The results suggest that existence of two possible distinct mechanisms which control metastatic growth: the local tumor might exert non-immunologically, an inhibitory effect on its lung metastases, and the spleen, possibly via suppressor lymphocytes, may suppress an immune effector activity against the tumor metastases, an activity which is manifested following splenectomy.

Animals↗
PubMed1981

Involvement of the spleen in murine B cell differentiation.

Experiments were performed to study the influence of neonatal and adult splenectomy on B cell differentiation in mice. Lymph node cells of both groups were found to contain a significantly higher proportion of Ig-bearing cells. Moreover, these cells expressed a higher density of membrane Ig and a higher IgM/IgD ratio. In addition, the response of these cells to different polyclonal B cell activators, especially dextran sulfate, was much higher than the response of the sham-operated controls. Similar experiments were carried out in splenectomized and control animals that were lethally irradiated and reconstituted with different hemopoietic cell sources. The same pattern of results was obtained, except when reconstituting the irradiated animals with fetal liver cells. These experiments, which were performed at long time intervals post splenectomy, show that in the absence of the spleen, there is an accumulation of less mature B cells in the periphery implying an active role of the spleen in at least certain differentiation steps of the B cell lineage.

Animals↗
PubMed1981

Involvement of the spleen in the control of the immunogenic and phagocytic function of thioglycollate-induced macrophages.

The immunogenic capacity of thioglycollate-induced peritoneal macrophages of adult splenectomized animals was compared to that of macrophages of sham-operated controls. Macrophages from splenectomized animals were found to be impaired in their function as antigen-presenting cells, both in the education of virgin initiator T lymphocytes and in the stimulation of antigen-specific T memory cells. Macrophages from splenectomized animals were also severely impaired in their phagocytic capacity, as assessed in an opsonin-dependent bacterial phagocytosis assay. However, they were not impaired in their ability to pinocytose soluble keyhole limpet hemocyanin. These results indicate that the spleen may play a decisive role in controlling the differentiation of peritoneal macrophages.

Animals↗
PubMed1981

Defective induction of antigen-reactive proliferating T cells in B cell-deprived mice.

Mice were injected from day of birth onward with rabbit anti-mouse IgM antiserum or purified rabbit anti-mouse IgM antibodies. These mice completely lacked Ig-positive cells or serum Ig, as analyzed by specific fluoresceinated antibodies on the fluorescence-activated cell sorter (FACS-II), by polyclonal B cell mitogens and by specific precipitation in agar. These animals were then primed in vivo by antigen emulsified in complete Freund's adjuvant, and, subsequently, their draining lymph nodes were tested for their T cell proliferative responses in vitro, to the relevant antigen and were found to be severely impaired. However, the antigen-presenting capacity of both spleen cells and thioglycollate-induced peritoneal cells was found to be intact.

Animals↗
PubMed1981

Metastatic properties conferred on nonmetastatic tumors by hybridization of spleen B-lymphocytes with plasmacytoma cells.

The P3-NSI/1-Ag4-1 (NSI) plasmacytoma, when transplanted sc in syngeneic BALB/c mice, grows locally without forming spontaneous metastases. We tested whether somatic hybridization of the NSI cells with spleen B-lymphocytes would render them metastatic in (C57BL/6 X BALB/c) F1 mice. We found that the hybridomas thus produced generated spontaneous metastases with distinct organ specificities. Some hybridomas produced metastases in both liver and spleen, whereas others produced metastases in only the liver. Cells derived from spleen-and liver-seeking hybridomas, when transplanted sc, produced tumors that metastasized to both the liver and spleen. Tumor cells derived from spleen metastasis produced, on transplantation, a tumor that generated spleen metastasis of a larger mass than did tumors derived from liver metastases. Cells derived from liver-seeking hybridomas metastasized to only the liver. Similar patterns of organ specificity were observed after iv injection of the hybridoma cells. The spleen seemed to play determining role in controlling the production of liver metastases by hybridomas that produced both liver and spleen metastases. Such hybridomas did not produce liver metastases when injected into splenectomized recipients. Hybridomas that were only liver-seeking did produce metastases in splenectomized recipients.

Animals↗
PubMed1980

Spontaneous remission of autoimmune encephalomyelitis is inhibited by splenectomy, thymectomy or ageing.

Experimental autoimmune encephalomyelitis (EAE) can be induced in genetically susceptible animals by injecting them with basic protein of myelin (BP) in a suitable adjuvant. EAE in adult Lewis rats is expressed clinically by acute paralysis and histologically by mononuclear cell infiltration of the central nervous system. Most rats spontaneously recover from EAE and show little or no damage to myelin. We report here that chronic progressive EAE with marked myelin lesions can be induced by a single injection of BP in complete Freund's adjuvant in intact 13-month old rats, or in 4-month old rats provided they have been splenectomized. Juvenile 2 1/2-month old rats recover spontaneously despite splenectomy. Thymectomy of young adult rats leads to relapsing EAE. These results illustrate that the clinical course of EAE is markedly influenced by age and integrity of immune organs. Furthermore, they provide an experimental model with features similar to those of chronic relapsing disease of the nervous system of man.

Aging↗
PubMed1980

H-2 gene products influence susceptibility of target thyroid gland to damage in experimental autoimmune thyroiditis.

The restriction of the pathogenesis of experimental autoimmune thyroiditis (EAT) by H-2 gene products was investigated. EAT was induced by injecting thyroglobulin extract plus adjuvant into F1 hybrid mice that had been implanted under the kidney capsules with thyroid glands originating from either the EAT-susceptible or -resistant parental strain mice. We found relative H-2 restriction of thyroid damage to those glands originating from the H-2 susceptible parental strain. H-2 restriction of damage at the level of the target thyroid gland implicates cytotoxic effector T lymphocytes as a pathogenic agent of EAT.

Animals↗
PubMed1980

Antigen-induced proliferation assay for rabbit T lymphocytes. I. Characteristics of the response.

An in vitro assay which measures specific antigen-induced proliferation of primed rabbit lymph node and peripheral blood cells is described. This response was found to be mediated by T cells, since it could be obtained with nylon-wool passed cells and cells which do not adhere to anti-Ig-coated plastic plates. The proliferative response was found to be highly antigen-specific and restricted to the draining lymph node if assessed up to 15 days post-priming. Purified T cells required antigen-pulsed accessory cells to proliferate. The proliferative response of peripheral blood lymphocytes was found to be low unless the lymphocytes were fractionated on insolubilized histamine. The histamine-adherent cells could suppress the above peripheral blood response, implying a certain regulatory role of suppressive cells in the periphery. The ease, reproducibility and specificity of the assay provides a simple method to evaluate the characteristics of a T-cell response in the rabbit.

Animals↗
PubMedDate not supplied

Measles is more prevalent in Crohn's disease patients. A multicentre Israeli study.

The question whether there is a transmissible pathogenetic agent as a cause for Crohn's disease, remains unanswered. Measles virus has been the subject of many intensive studies, in the attempt to find a role for it in the pathogenesis of inflammatory bowel disease. Whether an early infection with measles virus may predispose to Crohn's disease in later life is still not clear. We conducted a large scale multicentre study, in order to obtain sufficient data to answer this question. To do so, we compared inflammatory bowel disease patients, with Crohn's disease or ulcerative colitis, with two matched control groups: clinical controls, and community controls. A total of 531 patients, 271 with ulcerative colitis and 260 with Crohn's disease were interviewed, as well as 903 matched controls. Blood from 104 inflammatory bowel disease patients and 50 controls was tested for antibodies to measles virus. We did not find any differences related to measles vaccination, either in Crohn's disease or in ulcerative colitis. Exposure to measles in childhood was more frequent in Crohn's disease patients than in their controls, the difference being statistically significant (p < 0.05) in relation to community controls. The presence of IgG antibodies to measles virus was higher in patients with Crohn's disease than in patients with ulcerative colitis or controls (p = 0.084). Another observation of interest was the finding that Crohn's disease patients who had measles in childhood, more frequently had large bowel disease than those who had not had measles. These data lead us to postulate that there may be a role for measles infection in Crohn's disease, even if, at present, this role remains unclear.

Adult↗