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D Kaiserlian

Publications and source records attributed to D Kaiserlian.

72 records · Page 4Linked to original sources
PubMed1987

Epidermal cell-derived lymphocyte differentiating factor (ELDIF) inhibits in vitro lymphoproliferative responses and interleukin 2 production.

We have examined the biologic characteristics and immunologic properties of epidermal cell-derived lymphocyte differentiating factor (ELDIF), a lymphocyte differentiating factor produced by cultured human keratinocytes. The ELDIF was semipurified by a gel filtration procedure. This factor, which is distinct from prostaglandins, epidermal cell-derived thymocyte activating factor (ETAF), and the well-known thymic hormones (thymulin, thymopoietin, and thymosin alpha 1) did not exhibit any interleukin (IL)-1, IL-2, or IL-3 activity. It strongly inhibited in vitro lymphoproliferative responses of normal mouse spleen cells to phytohemagglutinin, concanavalin A, and lipopolysaccharide. This dose-dependent phenomenon was associated with a suppression of IL-2 production rather than any toxic effect. It can be concluded that ELDIF, a product of human epidermal cells, which displays in vitro T-cell differentiation and regulatory activities, could be of major importance in vivo in the control of cutaneous inflammatory reactions.

Animals↗
PubMed1986

Thymic hormone-containing cells. VII. Adrenals and gonads control the in vivo secretion of thymulin and its plasmatic inhibitor.

The influence of adrenals and gonads on the intrathymic production and the circulating level of thymulin was evaluated in young adult mice. Adrenalectomy (Adx) and gonadectomy (Cx) induce a temporary decrease of thymulin serum level. One simultaneously notes, as a compensatory phenomenon, an increase in the thymic content of the hormone-producing cells. The decrease of serum thymulin levels after Adx and Cx is at least partially due to the appearance of low m.w. thymulin-inhibitory molecules. The fact that thymectomy prevents the appearance of these inhibitors suggests that the effects of Adx and Cx could be explained by a negative control by sex hormones of the synthesis or activity of thymulin inhibitors produced or controlled by the thymus. Specific hormone replacement therapy of castrated/adrenalectomized animals normalized thymulin serum level and thymic content. Such correction was also spontaneously observed after 4 mo, suggesting that other mechanisms (e.g., an influence of the hypothalamus-hypophysis axis) might be involved in the endocrine control of thymic hormone secretion.

Adrenalectomy↗
PubMed1986

Epithelial cell heterogeneity in the guinea pig thymus: immunohistochemical characterization of four thymic epithelial subsets defined by monoclonal anti-keratin antibodies.

Keratins are a family of related polypeptides constitutive of the cytoskeleton of epithelial cells and are never found in nonepithelial tissues. Thymic epithelial cells (TEC), known to induce T cell differentiation, are the keratin-containing cells within the thymus. Using four monoclonal anti-keratin antibodies (KL1, KL4, AE2, AE3) directed against keratins of different molecular weight, we have investigated the guinea pig thymic epithelium. The immunohistochemical analysis of thymic cryostatic sections revealed that the keratin expression of TEC varied according to their location in the thymic lobula; the thymic cortex was specifically stained by AE3 whereas the thymic medulla and the subcapsular cortex were recognized by KL4. In addition, KL1 and AE2 exclusively labeled Hassall's corpuscles. The biochemical analysis of keratins extracted from the thymus showed that each TEC subset was characterized by an unique pattern of keratin polypeptides. This study extends the concept of thymic epithelium heterogeneity and suggests that anti-keratin antibodies which allow the typing of TEC subsets may be valuable tools for studying the differentiation of thymic epithelium and its in vitro function on T lymphocytes.

Animals↗
PubMed1986

The wasted mutant mouse. II. Immunological abnormalities in a mouse described as a model of ataxia-telangiectasia.

Ataxia-telangiectasia (AT) is a complex multiparametric disease associating oculocutaneous telangiectasias, cerebellar ataxia, elevated chromosomal aberration frequency and varied degrees of immunodeficiency. Recently a wasted mutant mouse (wst) has been described as an animal model of AT. We have looked in the wasted mutants for the presence of immune and endocrine abnormalities characteristic of AT. In contrast to the T cell immunodeficiency in AT, wasted mutants had a marked hypoplasia of all lymphoid organs, which affected both T and B lymphocyte subsets. The marked thymic atrophy appearing at the final stage of their disease did not modify the endocrine function of the thymic epithelium which produced normal levels of the thymic hormone thymulin. Although in vitro interleukin 2 (IL-2) production by splenic T cells in response to Con A was markedly diminished, these mice presented normal T and B cell proliferative responses to mitogens. Finally, no significant increase in serum alpha-fetoprotein level (a typical marker of AT) was found throughout the course of the disease. Although by many aspects, i.e. neurological disorder, chromosomal aberrations and early death, wasted mice presented similarities with human AT, major discrepancies in the typical features of immune abnormalities were found between the mouse model and the human disease.

Animals↗
PubMed1985

The wasted mutant mouse. I. An animal model of secretory IgA deficiency with normal serum IgA.

The wasted (wst) mutation was recently described as a spontaneous, recessive mutation leading to pathologic changes affecting both the neurologic and the immune systems of wst/wst homozygotes, which presented symptoms analogous to those observed in patients with ataxia-telangiectasia (A.T.). We studied the IgA system of wst/wst mutants and their normal littermates to determine whether IgA deficiency commonly found in A.T. patients was also affecting these mutants. Interestingly, although IgA plasma cells were totally absent from their entire (small and large) intestine, their serum contained a normal level of IgA with a normal ratio of monomeric vs polymeric IgA. The absence of gut IgA plasma cells was not due to malnutrition and was not compensated by the appearance of cells secreting any other isotypes. Studies at the precursor cell level showed the absence of IgA-specific B cell precursors in the Peyer's patches, whereas sIgA B cells and IgA plasma cells were found in normal numbers in the spleen of wasted mice. These data suggest that secretory and serum IgA may comprise distinct systems and that the wasted mutant mouse is a potential model for the study of the physiology and regulation of IgA production.

Animals↗
PubMed1984

In vivo and in vitro studies of thymulin in marginally zinc-deficient mice.

Thymulin (or serum thymic factor, FTS-Zn), a well-defined thymic hormone previously shown to be a nonapeptide binding the metal zinc, was studied in mice subjected to a long-term marginally Zn-deficient diet. In spite of the absence of thymic atrophy, we observed a significant decrease in the serum levels of thymulin as early as two months after the onset of treatment. However, these levels could be consistently restored after in vitro addition of ZnCl2. The analysis of thymuses from Zn-deficient mice showed that, despite the apparently normal network of epithelial cells, there was a progressive increase in the number of thymulin -containing cells (assessed by immunofluorescence with anti- thymulin monoclonal antibodies) that was already significant after two months of treatment. These results are in keeping with those of previous investigators, showing a specific, altered, thymic endocrine function following Zn deprivation. Nonetheless, our results strongly suggest that the nonactive Zn-deprived peptide is secreted under these experimental conditions. Furthermore, the fact that the augmented numbers of thymulin -containing cells were observed in the thymuses following a decrease in the peripheral thymulin (biologically active) brings further evidence for the existence of a feedback mechanism for the secretion of this hormone.

Animals↗
PubMed1984

Localization of zinc in the thymic reticulum of mice by electron-probe microanalysis.

Thymulin, a thymic hormone, is a nonapeptide requiring zinc for biological activity. It has been shown that epithelial cells, forming part of the thymic reticulum, secrete this hormone and/or store it within cytoplasmic vacuoles. X-ray electron-probe microanalysis (EPMA) has been used to detect zinc in the thymus. Low concentrations of zinc have been demonstrated in the dense granules contained in clear vacuoles of some epithelial cells in normal and ZnCl2-injected mouse thymuses, thus suggesting that the metal may be coupled to the peptide before the secretion of the hormone from the cells.

Animals↗
PubMed1984

Studies of the thymus in mice bearing the Lewis lung carcinoma. III. Possible mechanisms of tumor-induced thymic atrophy.

Adrenalectomy prevents thymic atrophy but not splenomegaly in mice implanted with Lewis Lung carcinoma cells. Surprisingly, the presence of the tumor does not lead to increased levels of corticosterone, which argues against an exclusive role of stress in the tumor-induced involution of the thymus. Interestingly, serum from tumor-bearing hosts in vitro displays strong cytolytic activity against normal syngeneic thymocytes. This thymocytotoxicity depends upon the stage of tumor development, i.e., the size of the local tumor, and is concomitant with the severe thymic atrophy. Treatment of donor mice with zinc chloride or excision of the local tumor, both of which have been shown to prevent this involution of the thymus, also abolishes the cytotoxic effect of the serum. The active component of the serum is a nonimmunoglobulin fraction of molecular weight greater than 25,000 Da. The possible mechanisms of tumor-dependent thymic atrophy as well as the in vivo relevance of this serum-mediated thymocytotoxicity are discussed.

Adrenalectomy↗
PubMed1983

Studies of the thymus in mice bearing the Lewis lung carcinoma. I. Thymic natural killer cell activity in 3LL tumor-bearing mice.

Natural killer (NK) cell activity of spleen and thymus was studied in Lewis lung carcinoma (3LL)-bearing mice. A high level of hydrocortisone-sensitive NK cell cytotoxicity was found in the thymus after excision of the primary tumor, but not in nonamputated mice. Conversely, splenic NK cell activity was diminished in nonamputated tumor-bearing mice and remained unmodified in amputated tumor-bearing mice. Excision of the primary tumor prevented tumor-induced thymic atrophy and splenomegaly. Histological study of the thymus revealed the presence of metastatic cells within the cortex. These data suggest that NK cells or their precursors are present in the thymus and can be triggered or unmasked in situ by tumor cells migrating from the primary tumor.

Agglutinins↗
PubMed1983

In vitro modulation of mouse natural killer (NK) cell activity by the serum thymic factor (FTS).

Previous studies indicated that the serum thymic factor (FTS) could modulate in vivo the level of splenic natural killer (NK) cell activity in mice. The present report shows that such an effect is also observed after a short term in vitro incubation of the effector cells with FTS. The regulatory effects of FTS result in an increase or a decrease of the splenic NK cell cytotoxicity depending upon the age and the mouse strain. Furthermore, FTS is able to enhance the NK cell activity of thymus and bone marrow cells which are known to be weakly reactive in NK cytotoxicity. Depletion experiments demonstrated that the FTS-induced increase of NK cell activity was not mediated by Thy 1+ cells nor macrophages, thus suggesting a direct action of FTS on the effector cells. Comparative studies using other thymic hormones revealed similar patterns of reactivity. These results favor the hypothesis of a close relationship between the thymus and NK cells.

Animals↗
PubMed1983

Studies of the thymus in mice bearing the Lewis lung carcinoma. II. Modulation of thymic natural killer activity by thymulin (FTS-Zn) and the antimetastatic effect of zinc.

Modulation of thymic natural killer (NK) cell activity by the serum thymic factor (thymulin or FTS-Zn) was demonstrated in mice carrying the Lewis lung carcinoma (3LL). Thymulin decreased the increased NK activity found in amputated (tumor) tumor-bearing mice and induced a significant NK activity in nonamputated mice, normally devoid of such activity. Zinc had no effect in either case. Histological studies revealed that zinc prevented the tumor-induced thymic atrophy. A clear-cut decrease in the number of lung metastases was observed in zinc-treated mice. This effect was suppressed by concomitant administration of thymulin to amputated mice. The thymic dependency of the anti-metastatic action of zinc as well as the mode of action of thymulin on NK cell activity in tumor-bearing animals is discussed.

Animals↗
PubMed1981

Prolongation of murine skin grafts by FTS and its synthetic analogues.

Synthetic serum thymic factor (FTS) and several of its analogues have been examined for immunoregulatory properties in a murine skin graft rejection model, including a syngeneic male-to-female system and an allogeneic system. In the syngeneic system, control animals with and without placebo had a mean graft survival time of 29 +/- 2 and 24 +/- 2 days respectively. Administration of FTS [10 ng bound to a carboxymethylcellulose (CMC) vehicle three times weekly until rejection] significantly delayed rejection (49 +/- 3 days). Similar although less striking results were obtained across the H-2 barrier. Several FTS analogues with retarded degradation were tested in the same system without CMC. All of them were as immunosuppressive as FTS. Interestingly, an analogue accelerated or delayed rejection depending on dosage, indicating the multiplicity of action of thymic peptides on the various T cell subsets.

Animals↗
PubMedDate not supplied

Epicutaneous and transcutaneous immunization using DNA or proteins.

Mucocutaneous surfaces are constantly exposed to an array of exogenous antigens including environmental proteins, peptides and low molecular weight and microbial pathogens. These tissues are covered by an epithelium which exerts both the role of a barrier, limiting the penetration of microbes and of hydrophylic antigenic moieties, but at the same time ensures that antigens which penetrate through the epithelium are rapidly captured and transported to draining lymph nodes for initiation of a specific immune response. Epithelial dendritic cells represent the immunocompetent cells responsible for the dynamic uptake and presentation of antigen entering peripheral tissues, and are unique in their efficiency in triggering the immune system and in initiating a primary immune response.

Administration, Cutaneous↗
PubMedDate not supplied

Heterogeneity of murine gut epithelium: three subsets defined by expression of dendritic cell markers.

Recent evidence has been provided for the immunological role of MHC class II molecules constitutively expressed by small intestinal epithelial cells (EC) in antigen presentation to specific T cells. Using immunohistochemical methods and antibodies to molecules expressed by dendritic cells (DC), considered as the most potent antigen presenting cell type, we observed that mature enterocytes of gut villi share common antigens with DC. Furthermore, these markers defined the heterogeneity of intestinal epithelium characterized by the presence of three EC subsets with distinct phenotype: immature crypt EC, Peyer's patch (PP) dome EC, and mature villi EC.

Animals↗