PubMed Health⌕ Search

Biomedical subjects

D Kaiserlian

Publications and source records attributed to D Kaiserlian.

At least 37 records · Page 2Linked to original sources
PubMed1997

Class I-restricted CTL induction by mucosal immunization with naked DNA encoding measles virus haemagglutinin.

We have investigated the class I-restricted CTL response specific for measles virus haemagglutinin (HA) in the spleens of mice immunized by various mucosal routes with a DNA plasmid carrying the HA gene (pV1j-HA). A single immunization with recombinant DNA injected in the buccal mucosa induced an HA-specific CTL response. Similarly, nasal immunization with the DNA vaccine induced primary CTLs against measles virus HA. Booster immunization did not enhance the CTL activity. Oral or intrajejunal immunization with the plasmid induced a CTL response of lower magnitude. However, this could be potentiated by co-administration of the mucosal adjuvant cholera toxin or cationic lipids (DOTAP). These data show that a CTL response can be generated by mucosal vaccination using DNA vaccines.

Animals↗
PubMed1996

Intestinal epithelial cell line induction of T cell differentiation from bone marrow precursors.

The mechanism whereby the intestinal microenvironment promotes T cell development in the absence of the thymus is unknown. We show that the murine intestine-derived epithelial cell line, MODE-K, can induce T cell differentiation marker expression in vitro on bone marrow (BM) T cell precursors. Three-color flow cytometry analysis of T-cell-depleted C3H BM mononuclear cells (MNC) after 4 days of coculture on monolayers of MODE-K indicated that approximately 25% of MNC expressed CD3 and TCR alpha beta. Of these CD3+ cells, 36% were CD3loCD4-CD8- double negative (DN), 34% were CD3loCD4+CD8 alpha beta+ double positive (DP), and the remainder were CD3hiCD4+CD8- or CD3hiCD4-CD8 alpha beta+ single positive (SP). In addition, the T cells which developed in coculture with MODE-K expressed the early T cell differentiation marker CD24 (heat-stable antigen). These T cells subsets did not develop when BM was cocultured with the LTA fibroblast cell line or in medium alone. Interestingly, preventing cell contact between MODE-K and BM by culturing in Transwell plates did not interfere with the development of T cells expressing the DN, DP, or SP phenotypes. Double-positive T cells did not develop if splenic MNC were cocultured with MODE-K. These results suggest that the intestinal epithelial environment can induce and support the T cell development from bone marrow precursors.

Animals↗
PubMed1996

Lack of oral tolerance but oral priming for contact sensitivity to dinitrofluorobenzene in major histocompatibility complex class II-deficient mice and in CD4+ T cell-depleted mice.

Oral tolerance is defined by immune unresponsiveness after oral administration of soluble antigens and by antigen-specific inhibition of peripheral immune responses induced by prior antigen feeding. The aim of this study was to investigate the implication of the major histocompatibility complex (MHC) class II presentation pathway to CD4+ T cells in oral tolerance of contact sensitivity (CS) to the hapten dinitrofluorobenzene (DNFB). We used MHC class II knockout (AB0/0) and invariant chain knockout (Ii0/0) mice, which have, respectively, a total or partial defect in class II-restricted activation of CD4+ T cells, as well as normal C57BL/6 mice depleted of CD4+ T cells by injection of a specific antibody. Intragastric administration of DNFB prior to skin sensitization induced specific inhibition of contact sensitivity to DNFB in A beta +/0 and Ii+/0 heterozygotes comparable to that observed in C57BL/6 mice. In contrast, no oral tolerance was observed in either MHC class II-deficient A beta 0/0 and Ii0/0 homozygote mutants or in syngeneic anti-CD4-depleted C57Bl/6 mice. Moreover, a single oral administration of DNFB, without skin sensitization, could prime A beta 0/0, Ii0/0 as well as anti-CD4-depleted C57BL/6 mice for DNFB-specific CS. These findings demonstrate that the class II/CD4 pathway is involved in oral tolerance manifested both as the inhibition of CS by hapten feeding prior to skin sensitization, and as immune unresponsiveness of normal mice to oral administration of hapten. Furthermore, our data provide evidence that a single oral feeding with DNFB is able to prime mice for hapten-specific CS, provided that the class II/ CD4 pathway is bypassed.

Administration, Oral↗
PubMed1996

Antigen presentation in the murine oral epithelium.

We have previously reported that the buccal mucosa can support delayed type hypersensitivity (DTH) reactions to contact sensitizers. In the present study, we show that cells isolated from the buccal epithelium are able to present soluble exogenous antigens to specific T cells. Single cell suspensions obtained by enzymatic dispersion of buccal epithelial sheets could present the native protein antigen hen-egg lysozyme (HEL) to the I-Ak-restricted CD4+ T-cell hybridoma specific for a.a 46-61 on HEL. T-cell activation resulted in interleukin-2 (IL-2) production which could be inhibited by anti-major histocompatibility complex (MHC) class-II antibodies of pertinent specificity. Immunohistochemical staining of whole buccal epithelial sheets revealed that all MHC II positive cells had a dendritic morphology and expressed ATPase activity, indicating that these cells represent a major antigen-presenting cell (APC) population in this tissue. Furthermore, single cell suspensions isolated from buccal epithelium (BEC) after local in vivo administration of either a native soluble protein, a synthetic dodecapeptide, or a contact sensitizer were able to activate antigen-specific T cells ex vivo. Kinetic analyses indicated that maximal APC activity in the oral epithelium occurred within 1 hr after local antigen administration, and had essentially vanished after 24 hr. Conversely, APC activity was undetectable in draining cervico-mandibular lymph node cell suspensions recovered 1 hr after local antigen injection but became manifest after 3-24 hr. These observations suggest that dendritic cells can acquire antigens in the buccal epithelium and migrate to draining lymph nodes where they present processed antigen to MHC class II-restricted T cells. This APC population may thus be a critical element in the initiation of Th1-driven DTH responses in the oral mucosa.

Animals↗
PubMed1996

Mucosal and systemic immune responses to measles virus haemagglutinin in mice immunized with a recombinant vaccinia virus.

The immune response to a vaccinia virus recombinant expressing the measles virus haemagglutinin (VV-HA) was compared after parenteral or mucosal immunizations in mice. Parenteral immunizations with 10(6) p.f.u. VV-HA induced HA-specific antibody-producing cells (IgG>IgA) and HA-specific class I-restricted cytotoxic T lymphocytes (CTL) in the spleen. In contrast, intranasal administrations of 10(6) p.f.u. of VV-HA induced HA-specific spot-forming cells in the spleen (IgG>IgA) and the lungs (IgA>IgG), and HA-specific CTL in the spleen. Co-immunization by the nasal route with VV-HA and cholera toxin enhanced HA-specific immune responses. Oral immunizations with 10(8) p.f.u. of VV-HA generated low numbers of HA-specific IgA-producing cells in the lamina propria of the gut, and a weak HA-specific CTL activity in the spleen and mesenteric lymph nodes. Oral co-immunization with VV-HA and cholera toxin greatly enhanced the level of HA-specific spot-forming cells in the lamina propria (IgA>IgG). Interestingly, intrajejunal immunizations with 10(8) p.f.u. VV-HA alone induced high levels of anti-HA IgG-producing cells in the spleen and anti-HA IgA-secreting cells in the lamina propria of the gut. These data show that (i) VV-HA by the nasal route is immunogenic and generates a measles-specific mucosal immune response in the lung, which represents the primary site of replication of measles virus and that (ii) VV-HA can also induce measles-specific immunity in the intestine provided that it is protected from degradation in the gastrointestinal tract, or that cholera toxin is used as an adjuvant.

Administration, Intranasal↗
PubMed1995

A role for stem cell factor and c-kit in the murine intestinal tract secretory response to cholera toxin.

The role of stem cell factor (SCF) and its receptor (c-kit) in the intestinal secretory response to cholera toxin (CT) was investigated using a ligated intestinal loop model in mice having mutations in the dominant white spotting (W) locus and the steel (Sl) locus. W/Wv mice, which express an aberrant form of the c-kit protein, failed to give an intestinal secretory response after luminal CT challenge. In contrast, W/Wv mice and their control littermates had equivalent intestinal secretory responses to Escherichia coli heat-stable enterotoxin (STa). Sl/Sld mice, which express only a soluble truncated form of SCF, also gave a significantly reduced intestinal secretory response to CT when compared to the secretory response of their littermate controls. The unresponsiveness of W/Wv mice to CT was restricted to the intestinal tract since these mice had foot pad swelling responses to CT challenge that were equivalent to their littermate controls. Restoration of mast cells in W/Wv mice by bone marrow transplantation of control littermate bone marrow did not reverse the CT-unresponsiveness of the intestinal tract. Histological evaluation of the gastrointestinal tract from W/Wv mice showed a normal distribution of enterochromaffin cells (ECC). CT challenge of either ligated intestinal loops from C57B1/6 mice or a mouse intestinal epithelial cell line (MODE-K) resulted in elevated levels of mRNA for SCF. MODE-K cells exposed to CT also had enhanced expression of c-kit. Finally, fluid obtained from CT-challenged ligated intestinal loops from C57B1/6 mice contained significant levels of SCF. Taken together, the above results suggest that CT-induced intestinal secretory responses are dependent upon SCF-c-kit interactions. These interactions appear to be induced as a consequence of CT stimulation of the intestinal tract and may also play a role in the development or functionality of the enteric nervous system.

Animals↗
PubMed1995

Oral tolerance to haptens: intestinal epithelial cells from 2,4-dinitrochlorobenzene-fed mice inhibit hapten-specific T cell activation in vitro.

The mechanisms underlying the induction of immunological tolerance after feeding soluble exogenous antigens, including proteins and haptens, are still unclear. Using a model of oral tolerance to the contact-sensitizing hapten 2,4-dinitrochlorobenzene (DNCB), we have compared the ability-of intestinal epithelial cells and of Peyer's patch APC to present DNCB in vitro or ex vivo after oral feeding, to specific peripheral lymph node T cells from DNCB-sensitized mice. In contrast to Peyer's patch APC, which induce efficient hapten-specific T cell activation upon exposure to the hapten either in vitro or in vivo, mature MHC class-II-positive intestinal epithelial cells were unable to induce T cell activation in either case. Interestingly, enterocytes from DNCB-fed mice exerted a dramatic inhibitory effect on the proliferative response of hapten-primed T cells in response to dinitrobenzene sulfonate presented by syngeneic spleen cells. This inhibitory effect, which was also observed with supernatant of intestinal epithelial cells from DNCB-fed mice, could be reversed by neutralizing anti-transforming growth factor (TGF)-beta antibodies. In addition, pre-incubation of hapten-sensitized T cells with enterocytes from DNCB-fed mice induced T cell anergy, which could be reversed by exogenous interleukin-2 or interleukin-4. These data demonstrate that intestinal epithelial cells activated in vivo by oral administration of DNCB are able to block proliferation of activated T cells through secretion of immunosuppressive cytokines such as TGF-beta. It is proposed that intestinal epithelial cells may play a significant role in oral tolerance by limiting T cell-mediated hypersensitivity responses.

Administration, Oral↗
PubMed1995

Interleukin-12 increases interleukin-4 production by established human Th0 and Th2-like T cell clones.

Interleukin (IL)-12 is a potent inducer of cell-mediated immunity: it favors the generation of interferon (IFN)-gamma-producing T cells, increases IFN-gamma production by T cells and natural killer cells and prevents the generation of a Th2 response in murine in vivo models. Nevertheless, the effects of IL-12 on an established Th2 response remain poorly documented. In the present paper, we analyzed the effect of IL-12 on the profile of lymphokines produced by established IL-4-producing Th0 and Th2-like human T cell clones (TCC) and by polyclonal T cells. We found that IL-12 (i) enhances, as previously reported, IFN-gamma production by Th0 TCC and, to a smaller extent, by Th2-like TCC, (ii) increases the proliferation of Th0 and Th2-like TCC and (iii) unexpectedly, synergizes with T cell receptor-associated or nonspecific stimuli in increasing IL-4 production by these TCC. Thus, IL-12 potentiates the production of IFN-gamma and also of IL-4 by established IL-4 producing TCC. Although IL-12 has been widely reported to induce a Th1 response and to prevent the development of a Th2 response in vivo, IL-12 may on the contrary potentiate an established Th2 response in humans.

CD4-Positive T-Lymphocytes↗
PubMed1995

Major histocompatibility complex class I-restricted CD8+ T cells and class II-restricted CD4+ T cells, respectively, mediate and regulate contact sensitivity to dinitrofluorobenzene.

Contact sensitivity (CS) is a form of delayed-type hypersensitivity to haptens applied epicutaneously and is thought to be mediated, like classical delayed-type hypersensitivity responses, by CD4+ T helper-1 cells. The aim of this study was to identify the effector T cells involved in CS. We studied CS to the strongly sensitizing hapten dinitrofluorobenzene (DNFB) in mice rendered deficient by homologous recombination in either major histocompatibility complex (MHC) class I, MHC class II, or both, and which exhibited deficiencies in, respectively, CD8+, CD4+, or both, T cells. MHC class I single-deficient and MHC class I/class II double-deficient mice, both of which have a drastic reduction in the number of CD8+ T cells, were unable to mount a CS response to DNFB. In contrast, both MHC class II-deficient mice and normal mice treated with an anti-CD4 monoclonal antibody (mAb) developed exaggerated and persistent responses relative to heterozygous control littermates. Furthermore, anti-CD8 mAb depletion of class II-deficient mice totally abolished their ability to mount an inflammatory response to DNFB. Removal of residual CD4+ T cells in class II-deficient mice by anti-CD4 mAb treatment did not diminish the intensity of CS. These data clearly demonstrate that class I-restricted CD8+ T cells are sufficient for the induction of CS to DNFB, and further support the idea that MHC class II-restricted CD4+ T cells down-regulate this inflammatory response.

Animals↗
PubMed1994

CD23/CD21 interaction is required for presentation of soluble protein antigen by lymphoblastoid B cell lines to specific CD4+ T cell clones.

Previous studies have documented a role for membrane-bound CD23 (the low affinity Fc epsilon RII) in presentation of alloantigens by B cells. The aim of the present study was to examine the involvement of cell surface CD23 in presentation of more conventional soluble protein antigens to T cells. We show that antibodies to CD23 and to its lymphocyte-associated second ligand, CD21, inhibit presentation of the cow's milk allergen casein, by autologous CD23+CD21+ B-EBV cell lines to casein-specific HLA-DP-restricted CD4+ T cell clones obtained from patients with either reaginic or enterophatic forms of cow's milk protein intolerance. Maximal inhibition was achieved when the antibodies were added at the initiation of the culture. The absence of specific inhibition by an anti-DR alpha monoclonal antibody (mAb) argues against a steric hindrance phenomenon impeding access of the T cell receptor to major histocompatibility complex class II molecules. Rather, anti-CD23 and anti-CD21 mAb-induced inhibition of antigen presentation seems to affect at least partly, heterotypic conjugate formation through CD23/CD21 interaction. Double immunofluorescence labeling of the T cell clones and antibody inhibition of T/B conjugate formation shows that functional CD23 and CD21 molecules are induced on T cells following contact with B-EBV cell lines. Taken together, these data indicate that CD23/CD21 interactions between T and B cells are required for presentation of soluble protein antigens by B-EBV cell lines to specific CD4+ T cells. The potential implications of these findings for allergen-specific T cell activation are discussed.

Antigen-Presenting Cells↗
PubMed1994

Rat cluster of differentiation 1 molecule: expression on the surface of intestinal epithelial cells and hepatocytes.

BACKGROUND/AIMS: Cluster of differentiation 1 (CD1) is a family of nonpolymorphic, major histocompatibility complex class I-like molecules with prominent expression in the liver and intestinal epithelium of humans and mice. Models of intestinal and hepatobiliary inflammation and experimental liver transplantation are conducted in the rat, yet nothing is known of CD1 expression in this species. METHODS: Monoclonal antibodies against murine CD1 were used to identify a rat CD1 homologue. Tissue messenger RNA expression was confirmed by Northern blot analysis with a murine CD1 complementary DNA probe. RESULTS: Immunoperoxidase staining detected CD1 in intestinal epithelial and liver cells but not in the thymus. Immunofluorescence of isolated hepatocytes and a rat fetal intestinal cell line, SLC-44, showed cell surface expression of CD1. Metabolic labeling and immunoprecipitation of the SLC-44 cell line and a mouse intestinal epithelial cell line, MODE-K, showed a protein of 55 kilodaltons. Immunoblotting of CD1 in isolated intestinal epithelial cells and hepatocytes showed a molecule of 55 kilodaltons. Northern blot analysis showed a single message of approximately 2.2 kilobases in hepatocytes. CONCLUSIONS: A CD1 homologue exists in the rat. Expression in the rat intestine and liver are similar to those in the human and mouse. The rat may be useful as a model for the study of CD1 function.

Animals↗
PubMed1994

Familial autoimmune enteropathy with circulating anti-bullous pemphigoid antibodies and chronic autoimmune hepatitis.

In a family of four children (two boys and two girls), the two brothers had severe, protracted watery diarrhea beginning at 2 and 3 weeks of life, respectively. Duodenal mucosa in both patients showed total villous atrophy and severe inflammatory infiltration of the entire bowel. The first patient also had lymphoid cell infiltration of the pancreas and died at 6 weeks of age. The second boy is alive at 2 years of age and is immunocompetent, but still receives total parenteral nutrition. Indirect immunofluorescence studies revealed circulating antibodies to enterocytes, smooth muscle, thyroid, and islet cells. Bullous pemphigoid antibodies (230 and 180 kd), specific for hemidesmosomal proteins and usually associated with a subepidermal blistering skin disease, were detected by direct and indirect immunofluorescence studies and by Western immunoblot. A diagnosis of autoimmune hepatitis was made, based on evidence of chronic active hepatitis and circulating anti-smooth muscle antibody. Immunosuppressive treatments induced partial clinical remission of the diarrhea but no resolution of the small bowel injury. At 16 months of age, remission of the diarrhea occurred, but persistent autoimmune hepatitis led us to maintain treatment with prednisone and azathioprine, and later with cyclosporine. In this child, as in other patients with autoimmune disease, the link between autoantibodies and organ damage remains uncertain but immunosuppressive treatment is indicated.

Autoantibodies↗