|
1
|
Hoang P, Dehennin JP, Li L, Sibille C, Geubel A, Vaerman JP. Human colonic intraepithelial lymphocytes regulate the cytokines produced by lamina propria mononuclear cells. Mediators Inflamm 2012; 6:105-9. [PMID: 18472843 PMCID: PMC2365852 DOI: 10.1080/09629359791794] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Using an in vitro autologous human system, the immunomodulatory function of colonic intraepithelial lymphocytes (IEL) on cytokine production by lamina propria mononuclear cells (LPMNC) has been investigated. In contrast to LPMNC, colonic IEL produced only low amounts of IL-10, interferon-gamma and interleukin-2. However, co-culture experiments (IEL + LPMNC) have shown that IEL can enhance the PHA-induced synthesis of IL-2 and interferon-gamma, but not IL-10 by LPMNC. Using a transwell filter culture system apparatus, this effect was shown not to require a cell-to-cell interaction. Thus, IEL in vitro may modulate the cytokine synthesis of LPMNC, through the production of soluble factors. This may prove highly relevant in the in vivo immune activation of the gastrointestinal mucosa.
Collapse
Affiliation(s)
- P Hoang
- Department of Gastroenterology University Hospital St-Luc Brussels B-1200 Belgium
| | | | | | | | | | | |
Collapse
|
|
2
|
Mayer L. A long needed re-evaluation of cells that suppress. Clin Immunol 2008; 127:268-9. [PMID: 18456561 DOI: 10.1016/j.clim.2008.02.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2008] [Accepted: 02/21/2008] [Indexed: 10/22/2022]
|
|
3
|
Xiao WB, Liu YL. Changes of CD8+CD28- T regulatory cells in rat model of colitis induced by 2,4-dinitrofluorobenzene. World J Gastroenterol 2003; 9:2528-32. [PMID: 14606090 PMCID: PMC4656534 DOI: 10.3748/wjg.v9.i11.2528] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the changes of CD8+ T subsets especially CD8+CD28- T regulatory cells in rat model of experimental colitis induced by 2,4-dinitrofluorobenzene (DNFB).
METHODS: The rat model of experimental colitis was induced by enema with DNFB. Ten days later, colonic intraepithelial and splenic lymphocytes were isolated from colitis animals (n = 16) and controls (n = 8). The proportion of CD8+ T cells, CD8+CD28+ T cells and CD8+CD28- T regulatory cells were determined by flow cytometry.
RESULTS: The model of experimental colitis was successfully established by DNFB that was demonstrated by bloody diarrhea, weight loss and colonic histopathology. The proportion of CD8+ T cells in either splenic or colonic intraepithelial lymphocytes was not significantly different between colitis animals and controls (spleen: 34.6% ± 7.24% vs 33.5% ± 9.41%, colon: 14.0% ± 8.93% vs 18.0% ± 4.06%, P > 0.05). But CD8+CD28- T regulatory cells from colitis animals were significantly more than those from controls (spleen: 11.3% ± 2.26% vs 5.64% ± 1.01%, colon: 6.50% ± 5.37% vs 1.07% ± 0.65%, P < 0.05). In contrast, CD8+CD28+ T cells from colitis animals were less than those from controls (spleen: 23.3% ± 6.14% vs 27.8% ± 9.70%, P = 0.06; colon: 7.52% ± 4.18% vs 16.9% ± 4.07%, P < 0.05). The proportion of CD8+CD28- T regulatory cells in splenic and colon intraepithelial CD8+ T cells from colitis animals was higher than that from controls (spleen: 33.3% ± 5.49% vs 18.4% ± 7.26%, colon: 46.0% ± 14.3% vs 6.10% ± 3.72%, P < 0.005).
CONCLUSION: Experimental colitis of rats can be induced by DNFB with simplicity and good reproducibility. The proportion of CD8+CD28- T regulatory cells in rats with experimental colitis is increased, which may be associated with the pathogenesis of colitis.
Collapse
Affiliation(s)
- Wen-Bin Xiao
- Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China
| | | |
Collapse
|
|
4
|
Abstract
The aim of this study was to examine in detail the low functional capacity of human intraepithelial lymphocytes (IELs) in response to phytohaemagglutinin (PHA) and CD3 ligation. Human IELs were extracted from jejunal mucosa obtained from patients undergoing gastric bypass operations for morbid obesity and compared to peripheral blood (PB) lymphocytes composed predominantly of CD8+ T cells. Calcium influx ([Ca2+]i) was analysed using Fura-2-loaded cells; IL-2 receptor expression was measured by immunofluorescence and flow cytometry; IL-2 binding was determined using radiolabelled IL-2; IL-2 production was quantified by ELISA; and apoptosis was detected with Apo 2.7 staining. Compared to naive PB CD8+ T lymphocytes, calcium influx by IELs was only transient with CD3 ligation and low in amplitude with PHA. IL-2 receptor expression was reduced after CD3 ligation, yet normal in numbers and affinity after PHA stimulation. Both cell types secreted similar amounts of IL-2. CD3 expression on IELs, but not PB CD8+ T cells, declined upon activation, due partly to incomplete reexpression after modulation. Little apoptosis was found. The partial activation of IELs in response to PHA and CD3 ligation, as manifested by diminished [Ca2+]i, resulted in a decline in CD3 expression.
Collapse
Affiliation(s)
- E C Ebert
- Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| |
Collapse
|
|
5
|
Eiras Martínez P, León Prieto F, Roldán Santiago E, Sánchez Muñoz L, Bootello Gil A, Roy Ariño G, Camarero Salces C, Baragaño González M, Asensio Vegas A, Eiras Martínez P. Linfocitos intraepiteliales en la enfermedad celíaca. An Pediatr (Barc) 2002. [DOI: 10.1016/s1695-4033(02)77787-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
|
|
6
|
Haslett PA, Corral LG, Albert M, Kaplan G. Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J Exp Med 1998; 187:1885-92. [PMID: 9607928 PMCID: PMC2212313 DOI: 10.1084/jem.187.11.1885] [Citation(s) in RCA: 439] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The efficacy of thalidomide (alpha-phthalimido-glutarimide) therapy in leprosy patients with erythema nodosum leprosum is thought to be due to inhibition of tumor necrosis factor alpha. In other diseases reported to respond to thalidomide, the mechanism of action of the drug is unclear. We show that thalidomide is a potent costimulator of primary human T cells in vitro, synergizing with stimulation via the T cell receptor complex to increase interleukin 2-mediated T cell proliferation and interferon gamma production. The costimulatory effect is greater on the CD8+ than the CD4+ T cell subset. The drug also increases the primary CD8+ cytotoxic T cell response induced by allogeneic dendritic cells in the absence of CD4+ T cells. Therefore, human T cell costimulation can be achieved pharmacologically with thalidomide, and preferentially in the CD8+ T cell subset.
Collapse
Affiliation(s)
- P A Haslett
- The Rockefeller University, New York 10021-6399, USA.
| | | | | | | |
Collapse
|
|
7
|
Abstract
HIV infection is likely to remain a significant medical and scientific problem well into the twenty-first century. During the first 15 years of the epidemic, much has been learned about the biology of HIV infection, but the majority of biomedical research has focused on the peripheral circulation. It is likely that the behavior of the virus within the unique immunologic environment of the intestinal mucosa differs from that which is observed in the periphery. Many clinical and epidemiologic features of HIV infection offer compelling reasons to encourage further examination of the mucosal immune system's role in AIDS pathogenesis. This article has touched on most of the significant observations concerning the mucosal immune system and HIV infection, and it is clear that much remains to be done. As mentioned earlier, the mucosal abnormalities observed in HIV infection are likely to have many causes. Careful evaluation of patients with early disease and fewer confounding variables may provide fresh insight into AIDS pathogenesis. Similarly, prospective evaluation of selected patient populations may be more informative in characterizing the progressive alterations in mucosal immune function than random cross-sectional studies of poorly defined groups. It is equally important for immunologic assessment to be correlated with nutritional and symptomatic evaluation. Finally, the success or failure of future antiretroviral therapies will be critically related to the impact of such agents on lymphoid reservoirs of HIV infection such as the gastrointestinal tract, which are at present refractory to treatment.
Collapse
Affiliation(s)
- I McGowan
- Division of Digestive Diseases, UCLA School of Medicine, USA
| | | | | | | |
Collapse
|
|
8
|
Radford-Smith G. Ulcerative colitis: an immunological disease? BAILLIERE'S CLINICAL GASTROENTEROLOGY 1997; 11:35-52. [PMID: 9192059 DOI: 10.1016/s0950-3528(97)90052-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Ulcerative colitis is an inflammatory disease of the large intestine of unknown aetiology. The nature of the inflammatory infiltrate together with the response to corticosteroids suggests that an abnormal immune response is at work. The key question of whether the immune system is responding to an abnormal breach in the mucosa due to another primary abnormality or whether the primary defect lies within the immune response itself has not been answered. Thus far, it is clear that both T and B cell compartments are involved in the persistence of inflammation but the initial interactions that take place in the mucosa in terms of antigen processing and presentation have not been adequately investigated. Those critical steps and potential defects that push T cells and B cells into a heightened state of activation need to be identified.
Collapse
Affiliation(s)
- G Radford-Smith
- Department of Gastroenterology, Royal Brisbane Hospital, Queensland, Australia
| |
Collapse
|
|
9
|
Chen D, Radford-Smith G, Dipaolo MC, McGowan I, Jewell DP. Cytokine gene transcription of human colonic intraepithelial lymphocytes costimulated with epithelial cells bearing HLA-DR and its inhibition by 5-aminosalicylic acid. J Clin Immunol 1996; 16:237-41. [PMID: 8840226 DOI: 10.1007/bf01541230] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
The objectives of this study were to activate human colonic intraepithelial lymphocytes at the transcriptional level with HLA-DR+ human colonic epithelial cell line (HT29) in synergy with CD3 monoclonal antibody and to investigate the molecular mechanism for the therapeutic effects of 5-aminosalicylic acid. Lymphocytes were isolated by a mechanical method from resected colon of 22 cases and then cocultured on 10 ng/ml CD3mAb immobilized plates with HT29 which had been induced to express MHC class II molecules by interferon gamma. Flow cytometry analysis suggested that the lymphocyte population had a CD4/CD8 ratio similar to that observed in intact tissue sections and that there was no HT29 contamination of the lymphocytes isolated again from cocultured cells. The activation of intraepithelial lymphocytes showed the gene transcription of interferon gamma and tumor necrosis factor alpha, as measured by means of the reverse-transcriptase polymerase chain reaction, and this activation was antagonized by 5-aminosalicylic acid. Thus, epithelial cells bearing HLA-DR are capable of enhancing CD3-induced activation of human colonic intraepithelial lymphocytes and subject to inhibition by 5-aminosalicylic acid, the active moiety of salicylates used in inflammatory bowel disease.
Collapse
Affiliation(s)
- D Chen
- Gastroenterology Unit, John Radcliffe Hospital, Oxford University, UK
| | | | | | | | | |
Collapse
|
|
10
|
Ohtsuka Y, Yamashiro Y, Maeda M, Oguchi S, Shimizu T, Nagata S, Yagita H, Yabuta K, Okumura K. Food antigen activates intraepithelial and lamina propria lymphocytes in food-sensitive enteropathy in mice. Pediatr Res 1996; 39:862-6. [PMID: 8726242 DOI: 10.1203/00006450-199605000-00020] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Morphologic and immunologic changes in the gut mucosa of food-hypersensitive mice, from a study model generated by feeding ovalbumin (OVA) to female BALB/c mice after intraperitoneal injection of cyclophosphamide (CY), were investigated in an effort to clarify the mechanisms of food-sensitive enteropathy. Villous atrophy, crypt hyperplasia, and increased numbers of intraepithelial lymphocytes (IEL) were confirmed in the antigen-challenged OVA-sensitive mice as seen in food-sensitive enteropathy in humans, whereas no significant morphologic changes were observed in the nontreated control group or groups treated with OVA or CY alone. IEL and lamina propria lymphocytes (LPL) were isolated from the intestinal mucosa before and after the antigen challenge, and surface markers were analyzed by FACScan. After the antigen challenge, the numbers of CD8+ cells increased among the IEL, and the occurrence of both CD4+ and CD8+ cells increased among the LPL. The numbers of Thy-1+ cells and TCR- alpha/beta + cells increased among both the IEL and LPL, and LFA-1 expression was enhanced in both of these lymphocyte populations. The proliferative response of IEL and LPL to OVA increased in a dose-dependent manner after the antigen challenge in the OVA-sensitive mouse model. These results indicate that IEL and LPL, possibly those that have migrated from peripheral blood, are activated by orally administered antigens and cause mucosal damage in the food-sensitive enteropathy.
Collapse
Affiliation(s)
- Y Ohtsuka
- Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan
| | | | | | | | | | | | | | | | | |
Collapse
|
|
11
|
Trejdosiewicz LK, Howdle PD. T-cell responses and cellular immunity in coeliac disease. BAILLIERE'S CLINICAL GASTROENTEROLOGY 1995; 9:251-72. [PMID: 7549027 DOI: 10.1016/0950-3528(95)90031-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Increasing evidence points to a direct role for T cells in the mediation of the coeliac intestinal lesion. There is good evidence for increased local T-cell reactivity, manifest as increased in T-cell activation in the lamina propria and T-cell proliferation in the epithelial compartment. A likely scenario is that gluten elicits antigen-specific responses by lamina propria T helper cells, probably of the Th1 (inflammatory-mediator) subtype, leading to secretion of pro-inflammatory cytokines. Such cytokines may have direct effects on intestinal enterocytes, as well as mediating indirect effects by upregulation of MHC antigens and by enhancing the activity of cytolytic T cells. Although gluten-specific IEL responses have not been demonstrated by intraepithelial T lymphocytes (IELs), increasing evidence suggests that IELs can act as cytolytic effector cells and hence are likely to exert enteropathic effects under the influence of pro-inflammatory cytokines.
Collapse
|
|
12
|
Yamashiro Y, Ohtsuka Y, Yabuta K. The regulation of intestinal hypersensitivity reactions to ovalbumin by omega-3 fatty acid enriched diet: studies of IEL and LPL in mucosal damage. ACTA PAEDIATRICA JAPONICA : OVERSEAS EDITION 1994; 36:550-6. [PMID: 7825462 DOI: 10.1111/j.1442-200x.1994.tb03245.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
In order to clarify the mechanisms of food-sensitive enteropathy, a food hypersensitive model was generated by feeding ovalbumin to female BALB/c mice after intraperitoneal injection of cyclophosphamide and morphological and immunological changes in the gut mucosa were investigated. Villus atrophy, crypt hyperplasia and increased numbers of intra-epithelial lymphocytes (IEL) were confirmed in this model, as seen in food-sensitive enteropathy in humans. Subpopulations of IEL and lamina propria lymphocytes were enumerated by immunohistochemical observation. CD8-positive cells were increased both in epithelium and lamina propria, whereas CD4-positive cells were decreased in lamina propria. We document here that orally administered food antigen actually induces food-sensitive enteropathy and mucosal damage is generated by lymphocytes that infiltrate the intestinal mucosa. We also investigated the effect of feeding an omega-3 fatty acid-enriched diet in this model and found that it was efficient in attenuating mucosal damage.
Collapse
Affiliation(s)
- Y Yamashiro
- Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan
| | | | | |
Collapse
|
|
13
|
|
|
14
|
Sadlack B, Merz H, Schorle H, Schimpl A, Feller AC, Horak I. Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell 1993; 75:253-61. [PMID: 8402910 DOI: 10.1016/0092-8674(93)80067-o] [Citation(s) in RCA: 1256] [Impact Index Per Article: 39.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Mice deficient for interleukin-2 develop normally during the first 3-4 weeks of age. However, later on they become severely compromised, and about 50% of the animals die between 4 and 9 weeks after birth. Of the remaining mice, 100% develop an inflammatory bowel disease with striking clinical and histological similarity to ulcerative colitis in humans. The alterations of the immune system are characterized by a high number of activated T and B cells, elevated immunoglobulin secretion, anti-colon antibodies, and aberrant expression of class II major histocompatibility complex molecules. The data provide evidence for a primary role of the immune system in the etiology of ulcerative colitis and strongly suggest that the disease results from an abnormal immune response to a normal antigenic stimulus.
Collapse
Affiliation(s)
- B Sadlack
- Institute of Virology and Immunobiology, University of Würzburg, Federal Republic of Germany
| | | | | | | | | | | |
Collapse
|
|
15
|
Dalton HR, Dipaolo MC, Sachdev GK, Crotty B, Hoang P, Jewell DP. Human colonic intraepithelial lymphocytes from patients with inflammatory bowel disease fail to down-regulate proliferative responses of primed allogeneic peripheral blood mononuclear cells after rechallenge with antigens. Clin Exp Immunol 1993; 93:97-102. [PMID: 8324909 PMCID: PMC1554734 DOI: 10.1111/j.1365-2249.1993.tb06503.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Human colonic intraepithelial lymphocytes from control subjects down-regulate the proliferative responses of primed allogeneic peripheral blood mononuclear cells on rechallenge with antigens or phytohaemagglutinin (PHA). In contrast, human colonic intraepithelial lymphocytes from patients with inflammatory bowel disease fail to down-regulate the proliferative responses of primed allogeneic peripheral blood mononuclear cells on rechallenge with antigens. These findings may be important in the development and maintenance of the mucosal immunological activation of inflammatory bowel disease.
Collapse
Affiliation(s)
- H R Dalton
- Gastroenterology Unit, Radcliffe Infirmary, Oxford, UK
| | | | | | | | | | | |
Collapse
|
|
16
|
Sachdev GK, Dalton HR, Hoang P, DiPaolo MC, Crotty B, Jewell DP. Human colonic intraepithelial lymphocytes suppress in vitro immunoglobulin synthesis by autologous peripheral blood lymphocytes and lamina propria lymphocytes. Gut 1993; 34:257-63. [PMID: 8432483 PMCID: PMC1373981 DOI: 10.1136/gut.34.2.257] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Human colonic intraepithelial lymphocytes have been shown to suppress the proliferation of autologous lamina propria lymphocytes and allogeneic peripheral blood mononuclear cells. This study has shown that, in vitro, intraepithelial lymphocytes suppress IgA and total immunoglobulin synthesis (but not IgG or IgM production) by autologous peripheral blood and lamina propria lymphocytes. This down regulation of IgA production is mediated by a soluble factor secreted by the intraepithelial lymphocytes. There is no difference in immunoglobulin down regulation by intraepithelial lymphocytes of control subjects and patients with inflammatory bowel disease.
Collapse
Affiliation(s)
- G K Sachdev
- Department of Gastroenterology, Radcliffe Infirmary, Oxford
| | | | | | | | | | | |
Collapse
|
|
17
|
Affiliation(s)
- H Scott
- Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), University of Oslo, Norway
| | | | | |
Collapse
|