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T T MacDonald

Publications and source records attributed to T T MacDonald.

At least 163 records · Page 9Linked to original sources
PubMed1988

HLA-DR expression in human fetal intestinal epithelium.

Villus epithelial cells in fetal human small intestine are HLA-DR- until 17 weeks gestation. At 18 weeks HLA-DR begins to be expressed in the epithelial cells, usually at the villus tips. Of 13 specimens examined between 18 and 22 weeks gestation, two were HLD-DR-, seven had HLA-DR expressed only at the villus tips and in four most of the villus epithelial cells were HLA-DR+. The epithelium overlying the Peyer's patches in fetal intestine was also HLA-DR+. T cells in explant cultures of fetal intestine were activated in situ using pokeweed mitogen. The local cell mediated immune reaction increased expression of HLA-DR on the villus and crypt epithelial cells. Organ culture supernatants from explants treated with pokeweed mitogen induced HLA-DR expression on the HT-29 epithelial cell line; an effect inhibited by antibody against human interferon gamma.

Epithelium↗
PubMed1988

Stimulation of mucosal T cells in situ with anti-CD3 antibody: location of the activated T cells and their distribution within the mucosal micro-environment.

Mucosal T cells in explants of human fetal small intestine (17-20 weeks gestation) in organ culture were activated in situ using monoclonal anti-CD3 antibody. Changes in the distribution of T cells within the mucosa, and their phenotype, were monitored by immunohistochemistry on frozen sections. Anti-CD3 stimulated T cells (as determined by expression of CD25) were predominantly in the lamina propria and were rarely seen in the epithelium. In control cultures, after 72 h, CD3+ IEL decreased to low numbers compared to day zero. However, in cultures treated with anti-CD3, IEL numbers were maintained and in some experiments significantly increased compared to day zero levels. At onset of culture 50-60% of CD3+ IEL were CD4-, 8-, and virtually all were HML-1+. The T cell infiltrate into the epithelium induced by activation of lamina propria T cells with anti-CD3 was also mostly CD3+, 4-, 8-, HML-1+. These experiments provide strong evidence that increases in IEL numbers can be a consequence of lamina propria T cell activation.

Antibodies↗
PubMed1987

Selective biopsy of human Peyer's patches during ileal endoscopy.

During routine lower gastrointestinal endoscopy of children for suspected chronic inflammatory bowel disease, it is possible to visualize lymphoid follicles (Peyer's patches) in the last few centimeters of the terminal ileum. Biopsy specimens have been taken from these Peyer's patches and the lymphoid cells have been isolated by collagenase digestion. The mean cell yield of Peyer's patch cells was 1.7 x 10(8) lymphocytes/g tissue. Isolated Peyer's patch cells were 26%-54% CD3+ (pan T cells), 14%-34% CD4+ (helper/inducer T cells), and 9%-17% CD8+ (suppressor/cytotoxic T cells). Twenty six percent to 48% of the Peyer's patch cells were B cells; less than 1% contained cytoplasmic immunoglobulin A. When stimulated in vitro with phytohemagglutinin or pokeweed mitogen, cells from Peyer's patches proliferated. The successful isolation of functional cells from Peyer's patches will now allow studies to be done at the afferent limb of mucosal immunoregulation in humans.

Adolescent↗
PubMed1987

Heterogeneity of non-lymphoid cells expressing HLA-D region antigens in human fetal gut.

Human fetal ileum contains an abundance of cells expressing HLA-D region (HLA-DR) antigens. In this study we characterized the HLA-DR positive cellular infiltrate in fetal ileum using a panel of monoclonal antibodies against cells of the macrophage/monocyte lineage. As well as anti-HLA-DR, the whole infiltrate was recognized by three of the antibodies in the panel studied: RFD1, reported to be an antibody to 'dendritic cells', leu3a which recognizes CD4 (an antigen expressed on helper/inducer T cells and macrophages), and PD7/26 which recognizes the leukocyte common antigen. The macrophage specific antibodies RFD7 and 3.9 stained fewer cells than the anti-HLA-DR. By sequential staining it was clear that most of the RFD7 positive macrophages in the fetal gut lamina propria were not recognized by 3.9 which is a broad specificity antimacrophage antibody in adult tissue. In contrast to this, more of the macrophages within the Peyer's patches of the fetal gut were recognized by 3.9 than by RFD7. In fetal lamina propria not all of the HLA-D region positive cells expressed macrophage markers and some expressed both markers associated with macrophages and 'dendritic' cells. Macrophages with different surface phenotypes were differentially distributed between the lamina propria and the primitive Peyer's patches; RFD7+, 3.9- macrophages were concentrated in the lamina propria whereas RFD7-, 3.9+ macrophages were abundant in Peyer's patches. Within the Peyer's patch lymphoid tissue RFD7+, 3.9- cells were present in the T cell zone whereas RFD7-, 3.9+ cells were concentrated in the dome region as they are in the adult. This suggests that functional heterogeneity of organized macrophage populations may occur in fetal ileum which is free of dietary and bacterial antigens.

Fetus↗
PubMed1986

Detection of chicken antibody to the protozoan parasite Eimeria tenella by antigen-coated microspheres.

A sensitive immunoassay for detecting antibodies to the protozoan parasite of poultry Eimeria tenella, has been developed. Microspheres coated with parasite antigen are reacted with antibody-containing chicken serum followed by a fluorescent labeled second antibody and analyzed by flow cytometry. The assay was used to demonstrate that chickens, vaccinated with E. tenella sporozoite antigen, showed significant elevations in serum antibody levels after exposure to infection compared to non-vaccinates. The assay is reproducible and because antigen-coated microspheres are stable for up to 4 weeks at 4 degrees C, a single batch can be used to analyze multiple serum samples.

Animals↗
PubMed1986

Lymphokine production by mitogen and antigen activated mouse intraepithelial lymphocytes.

Although most intraepithelial lymphocytes (IEL) in mouse small intestine bear surface markers classically associated with T lymphocytes, the T-cell nature of these cells remains controversial. In the present study IEL from normal mice, or from mice infected with the gut nematode Trichinella spiralis, were therefore tested for their ability to produce T-cell-derived lymphokines in response to in vitro stimulation with concanavalin A (Con A) or with specific worm antigens. The data show that Con A-stimulated IEL produce minimal amounts of IL-2, and intermediate levels of IFN-gamma and IL-3 in comparison to the levels produced by spleen T cells. The FDC-P2 cell line, which proliferates in response to both IL-3 and GM-CSF, was identified as the most sensitive and reproducible indicator of lymphokine activity in supernatants from mitogen-stimulated IEL from normal mice. IEL isolated from mice infected with T. spiralis also produced high levels of FDC-P2 growth factors when challenged in vitro with Trichinella-derived antigens; however, normal IEL did not respond to this stimulus. The data thus provide evidence that antigen-sensitive T cells can arise in (or migrate to) the gut epithelium during gut infection.

Animals↗
PubMed1986

Limit dilution analysis of mast cell precursor frequency in the gut epithelium of normal and Trichinella spiralis infected mice.

Previous studies have established that the gut nematode Trichinella spiralis induces a dramatic thymus dependent intestinal mastocytosis which peaks within 6 to 12 days after primary oral infection. It is not known, however, if the increase in gut mast cells results from the influx of mast cells or their precursors, or from the expansion and differentiation of mast cell precursors (MCP) that are normally present in the small intestinal epithelium. In the present study, the number of mucosal MCP in the intraepithelial lymphocyte (IEL) population and in bone marrow (BM) cells from normal and 4 day T. spiralis infected mice was compared by culturing the cells at limiting dilutions in medium containing interleukin-3 (IL-3). While the MCP frequency in IEL from infected mice was found to be significantly increased in comparison with that found in normal mice, the numbers of MCP in BM from the two groups were equivalent. Resident intraepithelial mucosal MCP therefore undergo a local expansion before the occurrence of an overt T dependent intestinal mastocytosis. This finding lends support to the view that local mucosal T cells are involved in regulating mast cell numbers in response to intestinal helminth infection.

Animals↗
PubMed1986

Yersinia enterocolitica infection in resistant and susceptible strains of mice.

We investigated natural resistance in mice to Yersinia enterocolitica, an enteric bacterial pathogen of humans, with a view to determine host genetic factors that are important in resistance. Most mouse strains studied (C3H/HeN, BALB/c, BALB.B, DBA/2, A, Swiss, and SWR) were highly susceptible to infection (50% lethal dose [LD50], 2 X 10(2) to 6 X 10(2) Y. enterocolitica administered intravenously [i.v.]). In contrast, C57BL/6 mice were highly resistant (LD50, 2 X 10(5) Y. enterocolitica administered i.v.). Resistance to i.v. Yersinia infection did not appear to be related to the Ity locus (which codes for resistance to Salmonella typhimurium and other pathogens) because Ityr mice (C3H/HeN, DBA/2, A, and SWR) were more susceptible to Y. enterocolitica than were Itys (C57BL/6) mice. In addition, because BALB.B mice (congenic to C57BL/6 mice at the H-2 locus) were susceptible, resistance was probably not H-2 linked. BALB/c X C57BL/6 F1 mice were intermediate in their resistance to Y. enterocolitica infection (LD50, 3 X 10(4) organisms administered i.v.), suggesting that resistance to Y. enterocolitica depends on a gene dosage affect or a resistance gene(s) interaction between susceptible and resistant parents. Further studies with C57BL/6 and BALB/c mice as prototype resistant and susceptible strains were undertaken. A time course study of Y. enterocolitica growth in various organs following i.v. infection revealed no strain difference in bacterial growth during the first 48 h of infection. Thereafter, however, C57BL/6 mice were capable of restricting Y. enterocolitica growth in all tissues (liver, lung, spleen, kidneys), whereas extensive bacterial proliferation occurred in BALB/c mice tissues. BALB/c mice were also more susceptible to oral Y. enterocolitica infection than were C57BL/6 mice, demonstrating increased mortality and greater numbers of bacteria in the Peyer's patches. Finally, whereas thymus-bearing C57BL/6 X BALB/c F1 mice were resistant to infection, athymic (nude) C57BL/6 X BALB/c F1 mice were susceptible. These studies provide a model to investigate natural immunity to enteric pathogens at mucosal surfaces, as well as provide the basis for clarifying the role of host genotype in Y. enterocolitica resistance.

Animals↗
PubMed1986

Functional characterization of Con A-responsive Lyt2-positive mouse small intestinal intraepithelial lymphocytes.

The surface phenotypes of resting vs Con A-stimulated intraepithelial lymphocytes (IEL) from mouse small intestine were directly determined by immunofluorescence with double labelling. Both Thy 1.2+, Lyt 2+ and Thy 1.2+ Lyt 2- IEL underwent blastogenesis and expressed interleukin-2 (IL-2) receptors. The Lyt 2+ subsets of IEL (which represent 80% of the total cells) were isolated by panning and shown to proliferate in response to Con A and IL-2, although the frequency of responsive precursors was dramatically lower than that seen in the splenic Lyt 2+ T-cell population (1 in 500 vs 1 in 8, respectively). Con A-stimulated Lyt 2+ IEL produced lymphokines supporting the growth of the interleukin-3 (IL-3)-dependent cell line DA-1, and of the FDC-P2 cell line that proliferates in response to both IL-3 and GM-CSF. The results therefore support the possibility that Lyt 2+ IEL act as inducers of local cell-mediated immune reactions by producing haematopoietic lymphokines.

Animals↗
PubMed1986

Modulation in vivo of Lyt 2 antigen expression on T cells by anti-Lyt 2 antibody: effects on Con A-induced unresponsiveness.

After a series of intraperitoneal injections of rat monoclonal anti-Lyt 2 antibody supernatant, BDF1 mice showed a loss of cells bearing Lyt 2 surface antigens but no reduction in the numbers of T cells in the spleen. With overnight culture in vitro, splenic T cells from anti-Lyt 2-treated mice regenerated surface Lyt 2, with the proportion of Lyt 2+ cells returning to control levels. Anti-rat IgG antibody was found in the serum of mice that had received the anti-Lyt 2 treatments. Modulation of the surface Lyt 2 antigens was demonstrable in vitro but only in the presence of mouse anti-rat IgG antibody. Functionally, this series of in vivo anti-Lyt 2 antibody treatments substantially reversed Con A-induced suppression of the anti-sheep red blood cell antibody response.

Animals↗
PubMed1986

The development of gut associated lymphoid tissue in the terminal ileum of fetal human intestine.

Lymphoid tissue in formalin fixed and snap frozen human fetal ileum has been studied using immunohistochemistry. At 11 weeks gestation clusters of cells expressing CD4 (leu-3a positive) are present in fetal ileum but these do not express CD3 (UCHT1 negative) and are probably macrophages. Aggregates of lymphoid tissue are apparent from 14 weeks gestation which contain T cells of helper/inducer and suppressor/cytotoxic phenotype. Both B and T cells are present at 16 weeks but with no cellular zonation. By 19 weeks, distinct follicles of B cells are present surrounded by T cells of helper/inducer and suppressor/cytotoxic phenotype. Follicular dendritic cells are also present within the B cell areas. The B cells at this age express surface IgM and IgD, C3b- and C3d-receptors. They also express the antigen CD5 which has been shown by others to be present on some fetal B cells but which is almost exclusively associated with T cells in the adult. HLA-D region antigens are present on apparently all of the cells within the fetal lymphoid follicles. The antigen on activated B cells, CD23 (recognized by MHM6), was present on some cells scattered within the B cell follicle. This is indicative of antigen independent B cell proliferation.

B-Lymphocytes↗
PubMed1986

T cell subclasses in fetal human ileum.

Lymphocytes within fetal human ileum were studied by immunocytochemistry to determine the appearance of T cells in human small intestine and the role of enteric antigen in the accumulation of cells of the suppressor/cytotoxic phenotype in the gut epithelium. In fetal human gut epithelium, cells bearing the pan T cell marker UCHT1 (CD3) were present in all of the specimens studied (11-19 weeks gestation). Of these, UCHT4+ (CD8, suppressor/cytotoxic phenotype) predominated over the leu3a+ (CD4, helper/inducer phenotype), although the differences were not as marked as in postnatal gut. UCHT1+ cells were also present in the lamina propria, frequently as small aggregates beneath the epithelium.

Child↗
PubMed1984

Functional properties of lymphocytes isolated from murine small intestinal epithelium.

Intraepithelial lymphocytes (IEL) were isolated from murine small intestine using a modification of previously published procedures. Analysis of IEL by immunofluorescence using monoclonal antibodies showed they were predominantly Lyt-2+ cells, with relatively few B cells or macrophages present. IEL cultured at sufficiently high cell densities proliferated in response to concanavalin A (Con A), phytohaemagglutin (PHA) and lipopolysaccharide (LPS). IEL were also capable of recognizing alloantigens in an in vivo graft-versus-host assay and in an in vitro mixed lymphocyte reaction. These studies therefore confirm that murine IEL contain cells with immunologic properties characteristic of typical T lymphocytes.

Animals↗