Search PubMed⌕ Search

Biomedical subjects

C Hauser

Publications and source records attributed to C Hauser.

At least 109 records · Page 6Linked to original sources
PubMed1994

Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation.

Interleukin-8 (IL-8) is a potent cytokine for recruitment and activation of neutrophils. To visualize its distribution in the intestinal mucosa and to understand better its possible role in the induction and promotion of inflammatory bowel disease, expression of the IL-8 gene was analyzed in resected bowel segments of 14 patients with active Crohn's disease or ulcerative colitis. In situ hybridization with IL-8 anti-sense RNA probes revealed strong and specific signals in the histologically affected mucosa. The number of cells expressing IL-8 gene correlated with the histological grade of active inflammation. In accordance with the characteristic histological signs of active disease, IL-8-expressing cells were diffusely distributed over the entire affected mucosa in patients with ulcerative colitis, whereas in patients with Crohn's disease, IL-8-expressing cells showed a focal distribution pattern. Cells expressing IL-8 were mainly located at the base of ulcers, in inflammatory exudates on mucosal surfaces, in crypt abscesses, and at the border of fistulae. Analysis of semi-serial sections pointed to macrophages, neutrophils, and epithelial cells as possible sources of this cytokine in active inflammatory bowel disease. We consistently failed to detect IL-8 messenger RNA in the mucosa of uninvolved bowel segments and in normal-appearing control mucosa of patients with colon cancer. In contrast, tissue specimens from two patients with acute appendicitis displayed IL-8-expressing cells in the mucosa. These results support the notion that IL-8 plays and important but nonspecific role in the pathogenesis of inflammatory bowel disease and that the production of IL-8 messenger RNA is restricted to areas with histological signs of inflammatory activity and mucosal destruction.

Adult↗
PubMed1993

Th2 cells mediate IL-4-dependent local tissue inflammation.

We investigated whether polyclonal murine Th1 and Th2 cells obtained after short term culture in vitro were capable of mediating tissue inflammation in vivo. Th cells were pulsed with mAb to the TCR/CD3 complex and injected into the footpads or ears of naive syngeneic recipient mice. Th1 induced delayed swelling that peaked at 24 to 48 h and lasted > or = 5 days. Th2-induced swelling peaked at 6 h and lasted < or = 48 h. Similar responses were also observed in athymic nude mice. Lesions with both Th1 and Th2 cells contained a predominant neutrophilic infiltrate at 6 h, and mainly mononuclear cells at 48 h. The inflammatory response with Th2 was blocked by cyclosporin A, by mAb to IL-4 or by soluble rIL-4R. The requirement for IL-4 was early and transient. Four alloreactive short term Th2 clones induced swelling in allogeneic recipients. mAb- and IL-4-dependent swelling responses were also observed with two long term Th2 clones. Our results demonstrate that Th2 cells mediate IL-4-dependent tissue inflammation, and strengthen the concept that Th2 cells play an important role in some T cell-dependent immune reactions and, possibly, in allergic disorders such as atopic dermatitis and allergic asthma.

Animals↗
PubMed1993

Lymphokine profiles in contact sensitivity induced by dinitrofluorobenzene and tolerance induced by dinitrothiocyanobenzene.

We determined the lymphokines involved in the immune response to epicutaneously applied dinitrofluorobenzene (DNFB), a sensitizer, and dinitrothiocyanobenzene (DNTB), a tolerogen. Hapten-dependent T-cell proliferation and production of interleukin-2, interleukin-3 and interleukin-4 by lymph node cells (LNC) in mice painted with these cross-reactive haptens were measured by specific lymphokine assays. Proliferation of LNC in tolerized animals was lower than in sensitized mice. LNC from DNTB-treated mice produced lower amounts of interleukin-2, interleukin-3 and interleukin-4 than cells from DNFB-painted mice. These results may explain hapten-specific tolerance induced by DNTB which results in deficient production of both type 1 T-helper cell (Th1) and type 2 T-helper cell (Th2) lymphokines in response to hapten re-exposure. Deficient interleukin-4 production by cells from tolerized mice was corrected by the addition of exogenous interleukin-2. The suppressor function of adoptively transferred T cells from animals tolerized with dinitrothiocyanobenzene may be related to a shift in the balance of Th1 and Th2 lymphokines in favour of the latter, since recipient T cells might provide the source of interleukin-2 that induces interleukin-4 production by donor T cells.

Animals↗
PubMed1993

Langerhans cells: structure, function and role in oral pathological conditions.

Langerhans cells (LCs) are dendritic bone marrow derived cells situated suprabasally in most stratified squamous epithelia, such as the epidermis and the epithelium of oral mucosa, including the gingiva. Langerhans cells are thought to act as antigen-presenting cells (APC) during induction of immune responses. The exact role of Langerhans cells in the oral mucosa is not fully understood although several investigations suggest that these cells are involved in reactions to antigen challenge under both normal and pathological situations. In this paper the structure, phenotypic markers and derivation of Langerhans cells are reviewed. In view of recent findings, the immunological characteristics and the implications of Langerhans cells in pathologic oral reactions are discussed.

Antigens, Surface↗
PubMed1992

[Livedo reticularis and multiple vascular occlusions in a patient with HLA-B27-negative spondyloarthrosis and antiphospholipid antibodies].

We report the case of a 74-year-old patient with HLA-B27 negative spondylarthropathy presenting with acute disseminated vascular occlusions. The presence of livedo reticularis prompted a search for antiphospholipid antibodies which were found to be markedly elevated. Histopathological examination revealed noninflammatory vascular obstruction. The clinical evolution was rapidly fatal in spite of corticosteroid treatment. Livedo reticularis can be an important diagnostic clue to various types of underlying disease. Increased levels of antiphospholipid antibodies have been associated with thrombosis and thromboembolism, especially in the context of autoimmune diseases such as systemic lupus erythematosus. This paper reports antiphospholipid antibody-associated noninflammatory vascular occlusions in a patient with HLA-B27 negative spondylarthropathy. The pathogenetic mechanism of antiphospholipid antibody-mediated vascular occlusions is not completely understood and optimal therapy remains to be defined.

Aged↗
PubMed1992

A common precursor for CD4+ T cells producing IL-2 or IL-4.

To investigate whether CD4+ T cells are predetermined to produce a given pattern of lymphokines, we have used a culture system that allows the controlled induction of either IL-2- or IL-4-producing CD4+ T cells. Single, freshly isolated murine CD4+ T cells were activated with Con A, rIL-2, and APC; the developing clones were split and then cultured for an additional 14 days with either rIL-2 alone or with rIL-2 and anti-CD3 stimulation. Subclones expanded in the presence of rIL-2 alone produced predominantly IL-2, although subclones derived from the same precursor and expanded in the presence of rIL-2 and a mitogenic antibody to CD3 released predominantly IL-4. Subclones expanded for 2 wk in the presence of rIL-2 plus a mitogenic mAb to CD3 released up to 60 times more IL-4 but only 1/90 the amount of IL-2 released by subclones derived from the same precursor cell and expanded with rIL-2. Both phenotypes can be derived from IL-2-producing precursor cells. These results demonstrate that IL-2-producing clones can be derived from the same cells as IL-4-producing clones and are most consistent with the view that the IL-2-producing Th1 or the IL-4-producing Th2 phenotype of a T cell clone is acquired during T cell differentiation and is not secondary to the expansion of distinct subpopulations that are predetermined to produce a specific cytokine pattern.

Animals↗
PubMed1992

Central role for TCR/CD3 ligation in the differentiation of CD4+ T cells toward A Th1 or Th2 functional phenotype.

Activated CD4+ T cells can be classified into distinct subsets; the most divergent among them may be considered to be the IL-2 and IFN-gamma-producing Th1 clones and the IL-4 and IL-5-producing Th2 clones. Because Th1 and Th2 clones can usually be detected only after several months of culture, we used conditions that modulate the IL-2 and IL-4 production in short term culture. Here we show that freshly isolated and subsequently in vitro-activated CD4+ T cells that were cultured for 11 days with rIL-2 and restimulated showed a IFN-gamma+ IL-2+ IL-3+ IL-4- IL-5- pattern. Because these cells were not capable of providing B cell help for IgG1, IgG2a, or IgE in an APC- and TCR-dependent T-B cell assay, they expressed a phenotype typical for most Th1 clones. In contrast, activated T cells that were cultured for 11 days with IL-2 plus a mAb to CD3 and then restimulated produced a IFN-gamma- IL-2- IL-3+ IL-4+ IL-5+ pattern. These cells were capable of providing B cell help for IgG1, IgG2a, and IgE synthesis and thus presented a phenotype typical for Th2 clones. Similar results were observed when mitogenic mAb to Thy-1.2 or to framework determinants of the alpha beta TCR were used. The induction of Th1- and Th2-like cells did not depend on the relative expression of CD44 or CD45 by the T cells before activation in vitro. Because the incubation of activated T cells with anti-CD3/TCR mAb induced high unrestricted lymphokine production, the latter might be responsible for the Th2-like lymphokine pattern observed after restimulation. To address this point, TCR V beta 8+ and V beta 8- T cell blasts were co-cultured in the presence of mAb to V beta 8. After restimulation, V beta 8+ cells had a IL-4high IL-2low phenotype and V beta 8- cells had a IL-4low IL-2high phenotype. This demonstrates that TCR ligation but not lymphokines alone are capable of inducing Th2-like cells, and this points out a central role for the TCR in the generation of T cell subsets.

Animals↗
PubMed1992

T cells from atopic individuals produce IgE-inducing activity incompletely blocked by anti-interleukin-4 antibody.

We investigated peripheral blood B and T lymphocyte functions in atopic individuals. B cells were co-cultured with mutant EL4 thymoma cells in the presence of a standard T cell supernatant (T-SN) with or without exogenous interleukin (IL)-4. IgE secretion in this assay was found to be IL-4 dependent, but not significantly different for atopic patients (n = 25) vs. normal controls (n = 25). Phytohemagglutinin plus phorbol 12-myristate 13-acetate (PHA+PMA)- induced T-SN from patients or controls was tested on normal B cells in the same assay system (in the absence of exogenous IL-4). Compared to the controls, the IgE-inducing activity was significantly increased for patients with asthma or allergic rhinitis (n = 12; p less than 0.005) but not for patients with atopic dermatitis (n = 13). The difference between the asthma or allergic rhinitis vs. the atopic dermatitis groups was significant (p greater than 0.05). Since the assay was not inhibited by interferon (IFN)-gamma, this difference can not be attributed to IFN-gamma concentrations. Other T cell activities may be different between the patient groups or atopic T cells from the respiratory mucosa may recirculate more than those from the skin. In any case, the T cells rather than the B cells were found to be abnormal in atopic individuals. If atopic T cells were stimulated with PHA+PMA not as immediately but after a resting period of 48 h in culture medium alone, the IgE-inducing activity, but not the total Ig-inducing activity or the IL-2 secretion, disappeared. In addition, a mean of 37% of the IgE-inducing activity (range of 13% to 79% for five very active T-SN) was not inhibited by an anti-IL-4 antibody which neutralized exogenous IL-4, indicating a participation of factors capable of bypassing the requirement for IL-4 for the IgE response.

Antibodies, Monoclonal↗
PubMed1992

Epidermal and splenic antigen-presenting cell function in a retrovirally induced murine immunodeficiency syndrome (MAIDS).

Since alterations of epidermal Langerhans cells (LC) have been observed in humans infected with HIV, we investigated the morphology and function of these cells in murine acquired immunodeficiency syndrome (MAIDS), a murine model closely resembling human AIDS. The number as well as the shape of dendritic MHC class II+ cells from ear skin of C57BL/6 mice were similar in normal and infected animals. In mixed epidermal cell (EC) lymphocyte cultures, EC from infected mice and from normal mice stimulated allogeneic T cell proliferation to the same extent. In contrast to T cells from normal mice, however, T cells from infected mice did not respond to allogeneic spleen cells, confirming the presence of a T-cell defect in MAIDS. Subcutaneous injection of syngeneic mice with trinitrophenyl-modified MAIDS EC resulted in delayed ear swelling responses after challenge that were equivalent to those induced by hapten-modified EC from normal mice, suggesting that the contact sensitivity inducing potential of MAIDS LC was preserved. To investigate antigen presenting and processing function, EC and spleen cells were tested with the ovalbumin-specific IAb-restricted T cell hybridoma BO.17.10 and either ovalbumin 323-339 peptide or intact ovalbumin protein. MAIDS spleen cells had a reduced antigen presenting capacity compared with normal spleen cells, whereas EC from these mice showed the same processing and presenting capacity as normal controls. In summary, our results demonstrate that the frequency, morphology, level of MHC class II antigen expression and ability to process and present antigen is normal for LC from mice with MAIDS whereas the function of splenic T cells and APC from infected mice is significantly impaired.

Animals↗
PubMed1992

The interaction between Langerhans cells and CD4+ T cells.

The human skin is increasingly exposed to haptens and environmental protein antigens. Because Langerhans cells represent the outermost network of MHC class II+ antigen presenting cells in mammalians, we investigated their interaction with CD4+ T cells. Hapten-modified Langerhans cells induced proliferation and IL-2 production in naive resting CD4+ T cells. T cells activated in this manner and subsequently cultured with IL-2 mediated contact sensitivity in vivo and produced IL-2 but no IL-4 upon restimulation in vitro. Thus they corresponded to Th1 cells. Repeated stimulation with Langerhans cells induced a modulation of the lymphokine pattern: IL-2- and IL-4-producing Th0-like cells were identified after 3 to 4 rounds of restimulation; after > 5 rounds, Th2-like cells with an IL-4+IL-2- pattern and the capacity for inducing IgE synthesis in B cells was identified. Th2 cells were also recently found to mediate inflammatory tissue lesions containing a cellular infiltrate. This demonstrates that Langerhans cells may activate resting CD4+ T cells, Th1-, Th0- and Th2-like cells. It further shows that Langerhans cells may promote the differentiation of postthymic CD4+ T cells into subsets with distinct immune functions: Th1 cells which have the potential to mediate inflammatory reactions such as allergic contact sensitivity and Th2 cells which may be responsible for abnormalities associated with atopic dermatitis, such as elevated IgE and inflammatory skin lesions containing a cellular infiltrate.

CD4-Positive T-Lymphocytes↗
PubMed1992

How to better understand the angry back syndrome.

The angry back or excited skin syndrome consists of patch test reactions that are positive only when associated with adjacent or distant inflammatory skin lesions. Recent experiments in the mouse and man have provided the knowledge on the critical role of tumor necrosis factor in contact dermatitis as well as its importance for the induction of adhesion molecules. Based on these new findings we speculate on mechanisms that might explain this poorly understood clinical phenomenon.

Animals↗
PubMed1991

Tumor necrosis factor is a critical mediator in hapten induced irritant and contact hypersensitivity reactions.

We examined the role of cytokines in the cutaneous response to the application of trinitrochlorobenzene (TNCB) in both nonsensitized and sensitized mice, i.e., in the irritant reaction (IR) and contact hypersensitivity reactions (CH). When administered immediately before challenge, anti-tumor necrosis factor (TNF) antibody abrogated the ear swelling response in CH; antibody directed against interferon gamma or antibodies to both granulocyte/macrophage colony-stimulating factor and interleukin 3 (IL-3) had a partial inhibitory effect; anti-IL-2 receptor antibody had no effect. Anti-TNF prevented the various features of the CH, as seen on histological sections, e.g., leukocyte infiltration and hemorrhages within the dermis and keratinocytes necrosis. Anti-TNF antibody also prevented the IR. The presence of TNF mRNA was evaluated on Northern blots; TNF-alpha mRNA was detectable in an untreated ear, increased after the application of TNCB in nonsensitized mice, and was highest in sensitized mice. TNF mRNA accumulation, which was evident 0.5 h after hapten application and lasted greater than 72 h, was abolished by treatment with anti-TNF antibody, thus suggesting an auto-amplification of TNF production. The cellular origin of TNF mRNA was explored by in situ hybridization; basal keratinocytes showed the highest labeling, but TNF mRNA was also detectable in cells of the dermal infiltrate. After hapten (TNCB) application at sites susceptible (the ear) or resistant (the foot pad) to CH or IR, a close correlation was observed between TNF mRNA accumulation and the intensity of the inflammatory reaction. The major role played by TNF in both the CH and the IR explains the histologically similar aspects of these reactions and the extreme variability of these reactions at various anatomical sites.

Animals↗
PubMed1991

Lectin-mediated induction of IL-4-producing CD4+ T cells.

Cultured murine CD4+ T cells have been shown to differentiate into IL-2 or IL-4-producing subsets. The factors responsible for the development of CD4+ T cells which produce IL-2 but not IL-4 and cells capable of producing IL-4 but not IL-2 are unknown. Here we describe a system that allows the controlled induction of IL-2- or IL-4-producing T cells after one single round of activation. Freshly isolated CD8-depleted T cells were activated with various polyclonal T cell activators for 48 h, washed, and then expanded under different conditions. IL-2 and IL-4 production were induced by restimulation of T cells and were measured with CTLL cells that respond to both cytokines and mAb to IL-2 and IL-4. T cells produced mainly IL-2 and small amounts of IL-4 when restimulated after expansion culture for 12 days with rIL-2 alone. However, after expansion for 12 days in the presence of rIL-2 plus Con A, we observed a 30- to 100-fold up-regulation of IL-4 activity and a 100-fold down-regulation of IL-2 when assessed by responses of CTLL cells incubated with the supernatant of restimulated T cells and by responses of CTLL cells cocultured with restimulated cells. An increase of IL-4 and decrease of IL-2 was also observed when the results were based on the cell numbers at the beginning of the expansion culture. The induction of IL-4 and the down-regulation of IL-2 1) were not reproduced with alpha-methyl-mannoside-treated supernatant of Con A-stimulated spleen cells, 2) were not dependent on the presence of large numbers of APC, 3) did not result from differential consumption of lymphokines after restimulation, 4) were not due to a difference in the time course of IL-2 or IL-4 release in either T cell population, and 5) were obtained regardless of the agents used to activate or to restimulate the T cells. Because Con A remained detectable on the T cell surface and because expansion of activated T cells with IL-2 plus Con A for several days was necessary, our results indicate that mainly IL-4-producing CD4+ T cells can be induced by prolonged engagement of T cell surface molecules.

Animals↗
PubMed1991

Evidence suggesting involvement of interleukin-4 (IL-4) production in spontaneous in vitro IgE synthesis in patients with atopic dermatitis.

To investigate the regulatory role of interleukin-4 (IL-4) and interferon-gamma (INF-gamma) and their involvement in the abnormality of IgE synthesis in patients with atopic dermatitis (AD), we studied the effect of recombinant human IL-4 and INF-gamma, as well as blocking antibodies (Abs) to these lymphokines on spontaneous IgE synthesis by peripheral blood lymphocytes (PBLs) from patients with AD and from healthy control subjects. PBLs from patients with AD demonstrated elevated spontaneous IgE production that was not stimulated further by the addition of recombinant IL-4, whereas for the healthy control subjects, recombinant IL-4 increased spontaneous IgE production by PBLs. INF-gamma that has been previously demonstrated to antagonize the effect of IL-4 on IgE synthesis, decreased IgE production of patients with AD. Addition of Abs to INF-gamma did not change spontaneous IgE production for patients with AD or for healthy control subjects. Together with our observation that IL-4 Abs lowered the high spontaneous IgE production by PBLs from patients with AD, these results suggest that in AD, IL-4 production by lymphocytes, together with a lack of INF-gamma production, is at least partially responsible for the increased spontaneous IgE production.

Adolescent↗