- Email: [email protected]
Fc epsilon RII (low affinity IgE receptor) is expressed on human epithelial cells and upregulated by IL-4 and LPS
filtered to remove microbial particulates. Cell surface CDld expression was subsequently analyzed on the human IEC line, T84, both in the absence and presence of dissolved fecal material. Exposureof T84 cells to fecal water resultedin a markedinduction of CDld expression as determined by semi-quantative RT-PCR,fluorescence microscopy and cell surface ELISA using a CDld specific antibody (4_+0.6fold increase). In contrast to CDld, fecal components did not enhanceexpressionof MHC class I or ICAM-1, an adhesion molecule. ElevatedCDld expression was detected by 12 hours and reached maximal levels by 72 hours of exposure. Upregulation of CDld was also consistent amongst fecal preparations isolated from different individuals. Preincuhation of fecal samples at 80°C for a period of 10 minutes completely abolished its ability to induce upregulationof CDld. Separationof fecal material into hydrophobic and aqueousphases by chloroform extraction and C18 column chromatographyresulted in a confinementof CDld inducingactivity to the non-lipid, aqueousfractions. Furtherbiochemical characterization revealedthe active component to be highly anionic at physiological pH, with a molecularweight between50 and lO0-kDa. Conclusions:Expressionof CDld on the surface of human IECs is influenced by a factor present within the lumen of the gastrointestinaltract. Determining the origin of the factor(s) may revealnovel roles for CDld in mediatinginteractions between the epithelial cell and the lumenal environment. Further steps to identify the CDld inducing component are discussed.
990 CD23 / Fc epsilon RII (Low Affinity IoE Receptor) Is Expressed on Hlamae F.pHhelial Cells and Unregulated by IL-4 and LPS Yahong Tu, Vincenza Di Leo, Sa'ed Salim, Johan D. Soderholm, John K. Marshall, Jan Irvine, Mary H. Perdue, McMaster Univ, Hamilton Canada Background: Our previous studies in models of food allergy (Yang et al, 2000; Yu ct al, 2000) have identified a novel mechanismfor enhancedtransepithelialantigen uptake in the intestine of sensitized rats and mice, involving IgE bound to its low affinity receptor, CD23 (Fc~ll), on enterocytes.This system results in the transport of specific antigen across epithelial cells in <2 rain. In addition, the quantity of intact antigen transported is several fold greater in sensitized rodents versus naive controls. Aim: The aim of this study was to examine CD23 expression in human intestinal epithelial cells. Methods: T84, HT29 and Caco-2 epithelial cell lines were grown _+ IL-4 and/or lipopolysaccharide (LPS). CD23 mRNA expression was determined by reversetranscriptional PCR and CD23 protein by western blotting. Human ileal biopsies were obtained by endoscopy and examined by immuno-histochemistp/. Results: CD23 mRNA was constitutively expressed in the three cultured human epithelial cell lines. The isoform of the expressedCD23 in epithelial cells was type b. Administration of IL-4 (10 ng/ml) increased the mRNA levels and elevated protein expression of CD23 by -3 fold in Caco-2 cells and -35 % in HT29 cells. LPS, a proinflammatory product of bacteria, dosedependently increased CD23 mRNA compared to controls. The peak of expression occurred at 10 mg/ml for HT29 and at 5 mg/ml for Caco-2 and T84 cell lines. The combination of IL4 and LPS together augmented CD23 mRNA expression. In the presenceof LPS (10 mg/ml) for 24 h, IL-4 treatment elevated CD23 mRNA in HT29 cells, reaching maximal expression at 8 h. For protein levels, LPS (10 mg/ml) increasedthe CD23 expression by - 2.5 fold in Caco-2 cells, -25 % in HT29 cells. In T84 cells, IL-4 (3 ng/ml) or LPS (3 mg/ml) increased CD23 protein expression by 3 fold respectively.With both IL-4 and LPS together, the CD23 protein expressionwas upregulatedby 4.7 fold as comparedto control. Morphologicalobservations of epithelialcell lines and human biopsies stainedwith anti-CD23,showedthat the CD23 protein was located mainly around the edge of the cultured cell clusters, and predomioately on the apical epithelial surface of the biopsies. Conclusions: Our evidence indicates that the low affinity receptor for IgE is upregulated by IL-4 and LPS in intestinal epithelial cells, and may function as an antigen transporter not only in food allergy but also in conditions involving bacteria/bacterial products, such as inflammatory bowel desease.
991 The Green Tea Polyphenol, (-)-eplgallocetechin-3-gallate BloCks Nuclear Factorkappa B Activation by Inhibiting IkappaB Kinase Activity in the Intestinal Epithelial Cell Line, IEC-6 Fajun Yang, Helieh Oz, Univ of Kentucky, Lexington, KY; Shirish Barve, Univ of Louisville, Louisville, KY; Willem J. Devilliers, Univ of Kentucky, Lexington, KY; Craig J. McClain, Univ of Louisville, Louisville, KY; Gary Varilek, Univ of Kentucky, Lexington, KY Background: Studies suggest that tea and its polyphenol derivatives have anti-cancer and anti-inflammatory effects possibly mediated by inhibition of the oxidative stress-sensitive transcription factor, nuclear factor-kappa B(NFKB). NFKB controls the expression of a wide variety of genes active in growth, innate immunity and inflammation. Studies show that inhibition of NFKB leads to a reduction in inflammatory responses as well as increased suseptibildy of cancer cells to apoptosis.A key control point in NFKBactivation is an upstream kinase, tKB kinase (IKK). Pharmacologicagents, such as mecalamine and salicylate inhibit IKK. In this study, we evaluatedwhether or not greentea polyphenolsinhibit NFKBby blocking IKK activity using the fetal rat intestinal epithelial cell line, IEC-6. Methods: We assessed IKK activity by detecting changesin phospborylationof an IKB~GST fusion protein. We compared an extract of green tea polyphenols (GrTP) to that of individual polyphenols and commonly studied antioxidants. Results. IEC-6 cells pretreatedwith GrTP (0-0.4 mg/ml) had diminished TNFa-induced IKK and NFKB activity. Of the various green tea polyphenols, (-)-epigallocatechin-3-gallate (EGCG) was the most potent inhibitor. We next examined whether EGCG inhibited activated IKK. In cytosolic extracts of TNFa-stimulated cells, EGCGinhibited phosphorylation of IKB~-GST (IC5o> 18/~M) consistent with inhibition of IKK activity. Using other polyphenols,we showedthat the gallate group found on EGCGwas essentialfor the observed inhibition. Antioxidants and polyphenols lacking the gallate group were ineffective in blocking activated IKK. Importantly, EGCGdecreasedIKK activity in cytosolic extracts of NFKB-inducing kinase (NIK) transiently transfected cells. This latter finding showed that our observations were not related to inhibition of non-specific kinases. Conclusion: EGCGinhibits IKK activity leadingto a reduction in NFKBactivation. This may explain in part how green tea polyphenols exhibit anti-cancer and anti-inflammatory effects.
A-188
992 Class Ib Expression Defect in IBD Epithelial Cells: Lack of Coordinate Regulation of CDld and the Epithelially Expressed CO8 Ligand, Op180. Ulani P. Perera, Anjlee Patel, Bana Jabri, Lloyd Mayer, Mount Sinai Medical Ctr, New York, NY Background: Recent studies have supported the concept that the mucosal immune system is regulatedin a manner distinct from systemic immunity. Among the models proposed, one statesthat intestinal epithelialcells (IECs)interact with regulatoryT cells. IECsexpressclassical restriction elements, class 1/11,as well as nonclassicalclass I molecules (class Ib). One class [b molecule, C01d, in conjunc~on with an accessory molecule, gp180, activates suppressor T calls. Aim: We wanted to determinewhether IECsexpressother class Ib molecules,whether gp180 and CDld are coordinately regulated, and whether these molecules are distributed uniformly throughout the colon and small intestine. Methods: We analyzedthe expressionof gp180 and class Ib moleculeson IECsobtainedfrom normal controls (n = 17),Crohn's Disease (CD) (n = 11) and UlcerativeColitis(UC) (n = 6) patients by mAb staining and flow cytometry (anti-gp180 - B9; anti-CDfd - D5 and 51.1.3; anti-HLA-E - 3D12; and anti-MICH8 - GD4). Background staining by isotype controls was subtracted. CDld expressionwas confirmed by RT-PCR. Results: Freshly isolated normal IECs expressed CDld =MICNMICB>>HLA-E by both % staining and mean channel fluorescence in all preparationstested. There was similar CDld expression in the fight colon/ileum and left colon (14 vs 17.65%-mAb 51.1.3 > D5). gp180 expression was similarly uniform. The presence of CDld mRNA was confirmed by RT-PCR, the level being greater in crypts vs surface IECs. Since we had documented a decreasein the expressionof gp180 in 18D patients, we used this system to analyzewhether there was coordinate regulation of CDld and gp180. Crohn's IECsexpressedvariable but low levels of CDld, which directly correlated with reduced gp180 expression. In contrast, in UC CDld expressionwas uniformly absent despite the presenceof gp180. In addition, there was no expression of MICNMICB and HLA-E. In CD, MICA/MICB expression was comparableto normal. Conclusions: gp180 and CDld are not coordinately regulated and there appears to be a generic defect in class Ib expression by UC IECs. Given the unique microenvironment of the intestine and unusual demands upon the mucosal immune system, the expression of distinct restriction elements (class Ib) and accessory molecules (gp180) may correlate with the activation of potent immunoregulatory T cells. The lack of expression of any of these components may result in an overactive immune response and intestinal inflammation.
993 IL-4 Enlmaces Transopithelial Antigen Transport by Stimulating CD23/Fc,-RII (Low Affinity ISE Receptor) Expression on Enterocytes of SensHized Mice. Unda C H Yu, Ping-ChangYang, Cecilia M. Berin, IDRP, McMaster Univ, Hamilton Canada; Daniel H. Conrad, Dept Microbiol & Immunol, Virginia Commonwealth Univ, Richmond, VA; Derek M. McKay, IDRP, McMaster Univ, Hamilton Canada;Abhay R. Satoskar, Dept Immunol & Infectious Dis, Harvard Sch Public Health, Boston, MA; Mary H. Perdue, IDRP, McMaster Univ, Hamilton Canada Our previous studies demonstratedenhancedtransepithelialtransport of antigen in the small intestine of sensitized rats. The transport system was shown to involve IgE bound to an IgE receptor on enterocytes. IL-4 is produced in excess in allergic conditions where it induces antibody isotype switching to IoE and upregulatesexpressionof CD23/Fc~II on B cells. AIM: This study was designed to examine the role of IL-4 and CD23 in enhancedtransepithelial antigen uptake using gene deficient mice and cultured mouse intestinal epithelial cells. METHODS: IL-4 -'-, CD23-'-, and appropriate + / + micewere activelysensitized(AS)to horseradish peroxidase(HRP); in addition, IL-4 "~+and IL-4 -~- mice were passively sensitized (PS) using untreated, IgE-depletedor IL-4-neutralizedserum obtainedfrom AS rats. Segmentsof jejunum were mounted in Ussing Chambersand challengedon the luminal surface with HRP. Tissues were fixed at 2 rain for EM; uptake was quantified by measuring the area of HRP-containing endosomes in enterocytes. Immunohistochemistry and RT-PCR were used to detect CD23 protein and transcdpt expressionon sensitizedmouse enterocytesand cultured mouse intestinal epithelial IEC-4 cells treated with IL-4. RESULTS:Luminal antigen uptake by enterocytes was enhanced in AS IL-4 +~+ mice and AS CD23+~+ mice, but not in AS IL-4-~- or CD23 mice, compared with unsensitized mice. Increasedantigen uptake was abolished in PS mice (both IL-4 +~* and IL-4 -j-) injected with serum depleted of either IgE or IL-4 compared with untreated serum. CD23 protein expressionwas detectedon enterocytesof sensitized,but not control, IL-4+~+ mice. The level of CD23 transcript was elevated in IEC-4 cells treated with IL-4 in a time-dependent manner. CONCLUSIONS:IL-4 is required for IgE/CO23-modlated enhanced antigen uptake in entemcytes of sensitized mice. The role of IL-4 in enhanced transepithelial antigen uptake is not solely by promoting IgE synthesis, but also involves upregulating expression of CD23 on enterocytes. Supported by CIHR EndosomalArea (I~)
IL'4+~ IL'4"~
CON
AS
PS
JOEH PS
0.38+0.03 0.29~0.06
4.31+1.13, 3.26~0.46, 0.25-~0.02 0.34+0.02 2.37+_0.25* 0.52~0.04
11.-4('1 P$ 0.71+0.04 0.37+0.04
N4
Human Intestinal Epithelium Expresses EBI3, A Potential Modulator Of The IL-12 Response. Christian Measer, Lars Eckmann, Univ of CA, San Diego, La Jella, CA; Mark P. Birkenbach, Eastern Virginia ~ch of Medicine, Norfolk, VA; Martin F. Kagnoff, Univ of CA, San Diego, La Jolla. CA
Background. Epstein-Barrvirus-indoced gene (E81)3 encodesa glycoprotein that is homologous to IL-12 p40 and can form a heterodimerwith the p35 subunit of IL-f 2. EBI3is expressed by monocyte-deriveddendritic cells, by cells with macrophege-and dendritic-cell-likemorphology in the inflamed intestinal lamina propda in ulcerative colitis, and by human placental
990 CD23 / Fc epsilon RII (Low Affinity IoE Receptor) Is Expressed on Hlamae F.pHhelial Cells and Unregulated by IL-4 and LPS Yahong Tu, Vincenza Di Leo, Sa'ed Salim, Johan D. Soderholm, John K. Marshall, Jan Irvine, Mary H. Perdue, McMaster Univ, Hamilton Canada Background: Our previous studies in models of food allergy (Yang et al, 2000; Yu ct al, 2000) have identified a novel mechanismfor enhancedtransepithelialantigen uptake in the intestine of sensitized rats and mice, involving IgE bound to its low affinity receptor, CD23 (Fc~ll), on enterocytes.This system results in the transport of specific antigen across epithelial cells in <2 rain. In addition, the quantity of intact antigen transported is several fold greater in sensitized rodents versus naive controls. Aim: The aim of this study was to examine CD23 expression in human intestinal epithelial cells. Methods: T84, HT29 and Caco-2 epithelial cell lines were grown _+ IL-4 and/or lipopolysaccharide (LPS). CD23 mRNA expression was determined by reversetranscriptional PCR and CD23 protein by western blotting. Human ileal biopsies were obtained by endoscopy and examined by immuno-histochemistp/. Results: CD23 mRNA was constitutively expressed in the three cultured human epithelial cell lines. The isoform of the expressedCD23 in epithelial cells was type b. Administration of IL-4 (10 ng/ml) increased the mRNA levels and elevated protein expression of CD23 by -3 fold in Caco-2 cells and -35 % in HT29 cells. LPS, a proinflammatory product of bacteria, dosedependently increased CD23 mRNA compared to controls. The peak of expression occurred at 10 mg/ml for HT29 and at 5 mg/ml for Caco-2 and T84 cell lines. The combination of IL4 and LPS together augmented CD23 mRNA expression. In the presenceof LPS (10 mg/ml) for 24 h, IL-4 treatment elevated CD23 mRNA in HT29 cells, reaching maximal expression at 8 h. For protein levels, LPS (10 mg/ml) increasedthe CD23 expression by - 2.5 fold in Caco-2 cells, -25 % in HT29 cells. In T84 cells, IL-4 (3 ng/ml) or LPS (3 mg/ml) increased CD23 protein expression by 3 fold respectively.With both IL-4 and LPS together, the CD23 protein expressionwas upregulatedby 4.7 fold as comparedto control. Morphologicalobservations of epithelialcell lines and human biopsies stainedwith anti-CD23,showedthat the CD23 protein was located mainly around the edge of the cultured cell clusters, and predomioately on the apical epithelial surface of the biopsies. Conclusions: Our evidence indicates that the low affinity receptor for IgE is upregulated by IL-4 and LPS in intestinal epithelial cells, and may function as an antigen transporter not only in food allergy but also in conditions involving bacteria/bacterial products, such as inflammatory bowel desease.
991 The Green Tea Polyphenol, (-)-eplgallocetechin-3-gallate BloCks Nuclear Factorkappa B Activation by Inhibiting IkappaB Kinase Activity in the Intestinal Epithelial Cell Line, IEC-6 Fajun Yang, Helieh Oz, Univ of Kentucky, Lexington, KY; Shirish Barve, Univ of Louisville, Louisville, KY; Willem J. Devilliers, Univ of Kentucky, Lexington, KY; Craig J. McClain, Univ of Louisville, Louisville, KY; Gary Varilek, Univ of Kentucky, Lexington, KY Background: Studies suggest that tea and its polyphenol derivatives have anti-cancer and anti-inflammatory effects possibly mediated by inhibition of the oxidative stress-sensitive transcription factor, nuclear factor-kappa B(NFKB). NFKB controls the expression of a wide variety of genes active in growth, innate immunity and inflammation. Studies show that inhibition of NFKB leads to a reduction in inflammatory responses as well as increased suseptibildy of cancer cells to apoptosis.A key control point in NFKBactivation is an upstream kinase, tKB kinase (IKK). Pharmacologicagents, such as mecalamine and salicylate inhibit IKK. In this study, we evaluatedwhether or not greentea polyphenolsinhibit NFKBby blocking IKK activity using the fetal rat intestinal epithelial cell line, IEC-6. Methods: We assessed IKK activity by detecting changesin phospborylationof an IKB~GST fusion protein. We compared an extract of green tea polyphenols (GrTP) to that of individual polyphenols and commonly studied antioxidants. Results. IEC-6 cells pretreatedwith GrTP (0-0.4 mg/ml) had diminished TNFa-induced IKK and NFKB activity. Of the various green tea polyphenols, (-)-epigallocatechin-3-gallate (EGCG) was the most potent inhibitor. We next examined whether EGCG inhibited activated IKK. In cytosolic extracts of TNFa-stimulated cells, EGCGinhibited phosphorylation of IKB~-GST (IC5o> 18/~M) consistent with inhibition of IKK activity. Using other polyphenols,we showedthat the gallate group found on EGCGwas essentialfor the observed inhibition. Antioxidants and polyphenols lacking the gallate group were ineffective in blocking activated IKK. Importantly, EGCGdecreasedIKK activity in cytosolic extracts of NFKB-inducing kinase (NIK) transiently transfected cells. This latter finding showed that our observations were not related to inhibition of non-specific kinases. Conclusion: EGCGinhibits IKK activity leadingto a reduction in NFKBactivation. This may explain in part how green tea polyphenols exhibit anti-cancer and anti-inflammatory effects.
A-188
992 Class Ib Expression Defect in IBD Epithelial Cells: Lack of Coordinate Regulation of CDld and the Epithelially Expressed CO8 Ligand, Op180. Ulani P. Perera, Anjlee Patel, Bana Jabri, Lloyd Mayer, Mount Sinai Medical Ctr, New York, NY Background: Recent studies have supported the concept that the mucosal immune system is regulatedin a manner distinct from systemic immunity. Among the models proposed, one statesthat intestinal epithelialcells (IECs)interact with regulatoryT cells. IECsexpressclassical restriction elements, class 1/11,as well as nonclassicalclass I molecules (class Ib). One class [b molecule, C01d, in conjunc~on with an accessory molecule, gp180, activates suppressor T calls. Aim: We wanted to determinewhether IECsexpressother class Ib molecules,whether gp180 and CDld are coordinately regulated, and whether these molecules are distributed uniformly throughout the colon and small intestine. Methods: We analyzedthe expressionof gp180 and class Ib moleculeson IECsobtainedfrom normal controls (n = 17),Crohn's Disease (CD) (n = 11) and UlcerativeColitis(UC) (n = 6) patients by mAb staining and flow cytometry (anti-gp180 - B9; anti-CDfd - D5 and 51.1.3; anti-HLA-E - 3D12; and anti-MICH8 - GD4). Background staining by isotype controls was subtracted. CDld expressionwas confirmed by RT-PCR. Results: Freshly isolated normal IECs expressed CDld =MICNMICB>>HLA-E by both % staining and mean channel fluorescence in all preparationstested. There was similar CDld expression in the fight colon/ileum and left colon (14 vs 17.65%-mAb 51.1.3 > D5). gp180 expression was similarly uniform. The presence of CDld mRNA was confirmed by RT-PCR, the level being greater in crypts vs surface IECs. Since we had documented a decreasein the expressionof gp180 in 18D patients, we used this system to analyzewhether there was coordinate regulation of CDld and gp180. Crohn's IECsexpressedvariable but low levels of CDld, which directly correlated with reduced gp180 expression. In contrast, in UC CDld expressionwas uniformly absent despite the presenceof gp180. In addition, there was no expression of MICNMICB and HLA-E. In CD, MICA/MICB expression was comparableto normal. Conclusions: gp180 and CDld are not coordinately regulated and there appears to be a generic defect in class Ib expression by UC IECs. Given the unique microenvironment of the intestine and unusual demands upon the mucosal immune system, the expression of distinct restriction elements (class Ib) and accessory molecules (gp180) may correlate with the activation of potent immunoregulatory T cells. The lack of expression of any of these components may result in an overactive immune response and intestinal inflammation.
993 IL-4 Enlmaces Transopithelial Antigen Transport by Stimulating CD23/Fc,-RII (Low Affinity ISE Receptor) Expression on Enterocytes of SensHized Mice. Unda C H Yu, Ping-ChangYang, Cecilia M. Berin, IDRP, McMaster Univ, Hamilton Canada; Daniel H. Conrad, Dept Microbiol & Immunol, Virginia Commonwealth Univ, Richmond, VA; Derek M. McKay, IDRP, McMaster Univ, Hamilton Canada;Abhay R. Satoskar, Dept Immunol & Infectious Dis, Harvard Sch Public Health, Boston, MA; Mary H. Perdue, IDRP, McMaster Univ, Hamilton Canada Our previous studies demonstratedenhancedtransepithelialtransport of antigen in the small intestine of sensitized rats. The transport system was shown to involve IgE bound to an IgE receptor on enterocytes. IL-4 is produced in excess in allergic conditions where it induces antibody isotype switching to IoE and upregulatesexpressionof CD23/Fc~II on B cells. AIM: This study was designed to examine the role of IL-4 and CD23 in enhancedtransepithelial antigen uptake using gene deficient mice and cultured mouse intestinal epithelial cells. METHODS: IL-4 -'-, CD23-'-, and appropriate + / + micewere activelysensitized(AS)to horseradish peroxidase(HRP); in addition, IL-4 "~+and IL-4 -~- mice were passively sensitized (PS) using untreated, IgE-depletedor IL-4-neutralizedserum obtainedfrom AS rats. Segmentsof jejunum were mounted in Ussing Chambersand challengedon the luminal surface with HRP. Tissues were fixed at 2 rain for EM; uptake was quantified by measuring the area of HRP-containing endosomes in enterocytes. Immunohistochemistry and RT-PCR were used to detect CD23 protein and transcdpt expressionon sensitizedmouse enterocytesand cultured mouse intestinal epithelial IEC-4 cells treated with IL-4. RESULTS:Luminal antigen uptake by enterocytes was enhanced in AS IL-4 +~+ mice and AS CD23+~+ mice, but not in AS IL-4-~- or CD23 mice, compared with unsensitized mice. Increasedantigen uptake was abolished in PS mice (both IL-4 +~* and IL-4 -j-) injected with serum depleted of either IgE or IL-4 compared with untreated serum. CD23 protein expressionwas detectedon enterocytesof sensitized,but not control, IL-4+~+ mice. The level of CD23 transcript was elevated in IEC-4 cells treated with IL-4 in a time-dependent manner. CONCLUSIONS:IL-4 is required for IgE/CO23-modlated enhanced antigen uptake in entemcytes of sensitized mice. The role of IL-4 in enhanced transepithelial antigen uptake is not solely by promoting IgE synthesis, but also involves upregulating expression of CD23 on enterocytes. Supported by CIHR EndosomalArea (I~)
IL'4+~ IL'4"~
CON
AS
PS
JOEH PS
0.38+0.03 0.29~0.06
4.31+1.13, 3.26~0.46, 0.25-~0.02 0.34+0.02 2.37+_0.25* 0.52~0.04
11.-4('1 P$ 0.71+0.04 0.37+0.04
N4
Human Intestinal Epithelium Expresses EBI3, A Potential Modulator Of The IL-12 Response. Christian Measer, Lars Eckmann, Univ of CA, San Diego, La Jella, CA; Mark P. Birkenbach, Eastern Virginia ~ch of Medicine, Norfolk, VA; Martin F. Kagnoff, Univ of CA, San Diego, La Jolla. CA
Background. Epstein-Barrvirus-indoced gene (E81)3 encodesa glycoprotein that is homologous to IL-12 p40 and can form a heterodimerwith the p35 subunit of IL-f 2. EBI3is expressed by monocyte-deriveddendritic cells, by cells with macrophege-and dendritic-cell-likemorphology in the inflamed intestinal lamina propda in ulcerative colitis, and by human placental