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Results for “Colitis, Lymphocytic”

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PubMed2003

Differential expression of homing receptor CD103 on lamina propria lymphocytes and association of CD103 with epithelial adhesion molecules in inflammatory bowel disease.

Intraepithelial lymphocytes play an important role in mucosal immunology, and are involved in the pathogenesis of inflammatory bowel disease. We studied expression of CD103 on mucosal lymphocytes with epithelial adhesion molecules in patients with inflammatory bowel disease. Surgical specimens of human colon were obtained from 12 patients with ulcerative colitis, 12 patients with Crohn's disease, and 5 controls. Frozen sections were cut and expression of CD103 on lymphocytes, E-cadherin, CD44V3, and CD44v6 on intestinal epithelium was studied. Frequency of CD103-positive intraepithelial lymphocytes did not differ among controls, patients with ulcerative colitis, and patients with Crohn's disease. The frequency of CD103-positive lamina propria lymphocytes was significantly higher in patients with Crohn's disease than in controls and patients with ulcerative colitis. The frequency of CD103-positive intraepithelial lymphocytes was significantly correlated with that of lamina propria lymphocytes in patients with ulcerative colitis. The frequency of CD103-positive intraepithelial lymphocytes was significantly correlated with epithelial E-cadherin expression but that of lamina propria lymphocytes was not. Differential up-regulation of CD103 expression on lamina propria lymphocytes in Crohn's disease may indicate differential humoral or cellular regulation in inducing CD103 molecules on lymphocytes in patients with this disease.

Antigens, CD↗

PubMed1993

Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice.

We describe the spontaneous development of inflammatory bowel disease (IBD) in several immunodeficient mouse strains created via gene targeting in embryonic stem cells. Chronic colitis was observed in T cell receptor (TCR) alpha mutant, TCR beta mutant, TCR beta x delta double mutant, or class II major histocompatibility complex (MHC) mutant mice, but not in recombination-activating gene RAG-1 mutant mice or nude mice kept in the same specific pathogen-free animal facility. This clinical pattern suggests that the disease requires the presence of B lymphocytes and the absence of class II MHC-restricted CD4+ alpha beta T cells. IBD in the mutant mice has some of the features of the human disease ulcerative colitis. Based on these results, we suggest that dysfunction of the mucosal immune system may underly the pathogenesis of some types of IBD in humans.

Aging↗

PubMed2005

Reduced susceptibility to dextran sulphate sodium-induced colitis in the interleukin-2 heterozygous (IL-2) mouse.

Summary Mice homozygous for an inactivation of the interleukin-2 (IL-2) gene develop a T-cell dependent colitis. Heterozygous (IL-2+/-) mice are clinically healthy but have been shown to express reduced levels of IL-2 in the colon. Splenocytes from the IL-2+/- mice had a poorer proliferative response to polyclonal T-cell activation and these mice have reduced numbers of intestinal regulatory T cells (CD4+ CD25+ cells) when compared to wild type mice. When exposed to dextran sulphate sodium (DSS) IL-2+/- mice showed a markedly reduced susceptibility to DSS-induced colitis. While DSS treatment caused a marked increase in both CD4+ and CD8+ colonic T cells expressing increased levels of IL-2, IL-4, and IL-10 in wild type mice none of these changes were seen in IL-2+/- mice. On the contrary, cytokine expression in intestinal T cells of IL-2+/- mice was actually reduced after DSS treatment. These results suggest that reduced levels of IL-2 leads to attenuated activation and function of intestinal T cells in IL-2+/- mice and a failure to react adequately to DSS exposure.

Animals↗

PubMed1985

Cells isolated from endoscopical biopsy specimens.

For a better understanding of local immunological factors in the pathogenesis of ulcerative colitis (UC), we isolated colonic mucosal lymphocytes (CML) from endoscopical biopsy specimens and studied their immunological characteristics. CML were isolated by a DTT-collagenase-cotton column method. Viability of isolated cells exceeded 90%, and the average yield per biopsy specimen was 1.2 +/- 0.6 X 10(4) (mean +/- SD). A large proportion of the CML isolated in this way were small lymphocytes and the numbers were higher in UC patients than in the controls. The percentage of T cells among the CML was higher in UC than in the controls, but the percentages of B cells did not differ. Peripheral blood lymphocytes from healthy controls showed very low levels of spontaneous synthesis of IgG, IgA, and IgM, but when cultured with PWM, these cells showed a high level of IgG and IgM synthesis but only a moderately elevated IgA production. In contrast, CML from healthy controls had a high level of spontaneous synthesis of IgG, IgA, and IgM; after culture with PWM, IgG synthesis roughly doubled and IgA synthesis increased tenfold compared with that of PBL. IgM synthesis was on the same level as in PBL. Although both PBL and CML cultured with PWM showed similar synthesis of IgG, IgA, and IgM in UC and healthy controls, the spontaneous synthesis of IgA and IgM in CML from patients with UC was approximately double that in the controls. Furthermore, in UC both PBL and CML had decreased Con A-induced suppressor-cell activity compared with controls. A defect of suppressor-cell activity and an increased number of T cells may play a role in the pathogenesis of UC.

Biopsy↗

PubMed2006

Cutting edge: Critical role for A2A adenosine receptors in the T cell-mediated regulation of colitis.

A(2A) adenosine receptors (A(2A)AR) inhibit inflammation, although the mechanisms through which adenosine exerts its effects remain unclear. Although the transfer of regulatory Th cells blocks colitis induced by pathogenic CD45RB(high) Th cells, we show that CD45RB(low) or CD25+ Th cells from A(2A)AR-deficient mice do not prevent disease. Moreover, CD45RB(high) Th cells from A(2A)AR-deficient mice were not suppressed by control CD45RB(low) Th cells. A(2A)AR agonists suppressed the production of proinflammatory cytokines by CD45RB(high) and CD45RB(low) T cells in association with a loss of mRNA stability. In contrast, anti-inflammatory cytokines, including IL-10 and TGF-beta, were minimally affected. Oral administration of the A(2A)AR agonist ATL313 attenuated disease in mice receiving CD45RB(high) Th cells. These data suggest that A(2A)AR play a novel role in the control of T cell-mediated colitis by suppressing the expression of proinflammatory cytokines while sparing anti-inflammatory activity mediated by IL-10 and TGF-beta.

Adenosine A2 Receptor Agonists↗

PubMed2006

Ameliorating effect of saporin-conjugated anti-CD11b monoclonal antibody in a murine T-cell-mediated chronic colitis.

BACKGROUND: Crohn's disease (CD) is an inflammatory bowel disease that is associated with several changes in the immune system, including an increased number of infiltrating macrophages. These macrophages release a variety of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) which are critically involved in the onset and the development of CD. The present study was performed to explore the initial involvement of macrophages in the development of T-cell-mediated chronic colitis. METHODS: The effects were evaluated of saporin-conjugated anti-CD11b monoclonal antibody (mAb) on the development of chronic colitis in severe combined immunodeficiency (SCID) mice induced by adoptive transfer of CD4(+)CD45RB(high) T cells as an animal model of CD. RESULTS: Significantly increased CD11b-expressing macrophages as well as CD4(+) T cells were found in inflamed colon from colitic mice. Administration of saporin-conjugated anti-CD11b mAb markedly ameliorated the clinical and histopathological disease. In vivo treatment with saporin-conjugated anti-CD11b mAb decreased CD4(+) T-cell infiltration in the colon and suppressed interferon-gamma (IFN-gamma) and TNF-alpha production by lamina propria CD4(+) T cells. CONCLUSIONS: Collectively, the present results suggest an initial role of macrophages in the pathogenesis of T-cell-mediated chronic colitis. Furthermore, the macrophage-specific targeting may be a promising strategy for therapeutic intervention in CD.

Animals↗

PubMed2004

CD4+ T cells from IL-10-deficient mice transfer susceptibility to NSAID-induced Rag colitis.

Products of arachidonic acid metabolism are important for mucosal homeostasis, because blockade of this pathway with an NSAID triggers rapid onset of severe colitis in the IL-10 knockout (IL-10(-/-)) model of IBD. Rag mice do not make T or B cells. This study determined whether reconstitution of Rag mice with T cells from IL-10(-/-) mice transferred NSAID colitis susceptibility. Rag mice were reconstituted by intraperitoneal injection with splenocytes from wild-type (WT) or IL-10(-/-) animals. Colitis was induced by using piroxicam and was graded histologically. Isolated lamina propria mononuclear cells (LPMC), lamina propria T cells, and LPMC depleted of T cells from reconstituted Rag mice were studied for cytokine production. Only animals reconstituted with IL-10(-/-) CD4(+) T cells and administered piroxicam developed severe colitis. LPMC from these colitic animals made IFN-gamma, whose production was dependent on T cells. Some IL-10 was produced but only from non-T cells. LPMC from the healthy Rag mice that were reconstituted with WT T cells and were piroxicam resistant made much more IL-10. This was mostly T cell dependent. In conclusion, only CD4(+) T cells from IL-10(-/-) animals leave Rag mice susceptible to NSAID-induced, Th1 colitis. Lamina propria T cells normally make large quantities of IL-10, suggesting that IL-10 from T cells may be protective.

Animals↗

PubMed2006

The S1P receptor modulator FTY720 prevents the development of experimental colitis in mice.

To evaluate the therapeutic effects of the new synthetic sphingosine-1-phosphate (S1P) receptor modulator, FTY720, we investigated how FTY720 affects the development of dextran sulfate sodium (DSS)-induced colitis and CD4+CD62L+ T cell transfer colitis. BALB/c mice were fed a chow containing 3.5% (wt/wt) DSS to induce colitis. The CD4+CD62L+ T cell transfer colitis was induced by an intraperitoneal injection of CD4+CD62L+ spleen T cells into recipient CB17 SCID mice. The FTY720 was administered by lavage at a dose of 0.3 mg/kg/day. FTY720 was effective in preventing the body weight loss in the DSS-colitis model and the CD4+CD62L+ T cell transfer model. The disease activity index, histological colitis score, and MPO activity were all significantly lower in FTY720-treated mice than in the non-treated mice. Microscopically, mucosal edema, cellular infiltration and epithelial disruption were much more moderate in the FTY720-treated mice than in the non-treated mice. In both colitis models, FTY720 prevented the infiltration of CD4+ T cells into the inflamed colonic lamina propria. In conclusion, the development of DSS-colitis and CD4+CD62L+ T cell transfer colitis were significantly attenuated by FTY720. Since FTY720 is an immunosuppressive product that does not modulate T cell functions, it could be useful in the treatment of IBD patients.

Animals↗

PubMed2006

The neutrophil/Th1 lymphocyte balance and the therapeutic effect of granulocyte colony-stimulating factor in TNBS-induced colitis of rat strains.

Intramucosal neutrophil infiltration is related to the activity of ulcerative colitis, and Th1 immunity is responsible for the onset of Crohn's disease. We examined the therapeutic effects of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) in the two types of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis of five rat strains. SD and DA rats showed much lower mRNA expression levels of endogenous G-CSF in lipopolysaccharide (LPS)-stimulated splenocytes than did Lewis, F344, and BN rats. On day 7 after anal instillation of TNBS, SD and DA rats demonstrated massive lymphocyte infiltration with an interferon-gamma (IFN-gamma) mRNA upregulation, whereas Lewis, F344, and BN rats showed an intense submucosal neutrophil accumulation with high tumor necrosis factor-alpha (TNF-alpha) mRNA levels. A 5-day course of rHuG-CSF pretreatment (250 microg/kg/day, s.c.) reduced the elevated levels of both cytokines. The treatment improved the survival rate of DA and reduced the degree of body weight loss of SD, while not significantly influencing the wasting disease of other strains. Interleukin-10 (IL-10) mRNA levels were highly upregulated by rHuG-CSF treatment on day 1 in the neutrophil-dominant lesions of F344 but not in the Th1-type lesions of SD, and IL-12p35 mRNA levels were downregulated in both. A supply of G-CSF prevents the onset of Th1-type TNBS colitis and does not deteriorate neutrophil-dominant chronic colitis in hosts showing higher expression of endogenous G-CSF.

Animals↗

PubMed1995

Phenotypic and immunoregulatory analysis of intestinal T-cells in patients with inflammatory bowel disease: evaluation of an in vitro model.

Although a disturbed immune response to constituents of the gut mucosa has been implicated in the pathogenesis of inflammatory bowel disease, the mechanisms are still unclear. Intestinal T-cells derived from gut biopsies were propagated in vitro as single and co-cultures under different experimental conditions prior to flow cytometry. Intestinal T-cell lines from inflamed mucosa (n = 69) showed a significant (P < 0.001) decrease in CD4+ T-cells compared to T-cells from normal (n = 49) and uninflamed (n = 29) tissue specimens. Co-culturing of inflamed and uninflamed mucosa led to a normalization of CD4+ T-cells in cultures derived from inflamed mucosa. Analysis of supernatants revealed a significantly (P < 0.001) increased secretion of IL-4 under co-culture conditions. Moreover, stimulation of cultures derived from inflamed mucosa with rIL-4 led to a significant (P < 0.001) increase in CD4+ T-cells, whereas anti-IL-4 antibodies or IFN-gamma supplementation of T-cells derived from uninflamed mucosa significantly (P < 0.001) reduced the CD4+ subset. Treatment with IFN-gamma and anti-IL-4 antibodies did not affect the phenotype of T-cells derived from inflamed mucosa. These data suggest that IL-4 might play a key role in the intestinal immune response. Furthermore, this in vitro system allows the investigation of mucosal immune mechanisms in more detail under standardized conditions.

Adolescent↗

PubMed2003

Therapeutic effect of anti-OX40L and anti-TNF-alpha MAbs in a murine model of chronic colitis.

Interaction of OX40 (CD134) on T cells with its ligand (OX40L) on antigen-presenting cells has been implicated in pathogenic T cell activation. This study was performed to explore the involvement of OX40/OX40L in the development of T cell-mediated chronic colitis. We evaluated both the preventive and therapeutic effects of neutralizing anti-OX40L MAb on the development of chronic colitis in SCID mice induced by adoptive transfer of CD4(+)CD45RB(high) T cells as an animal model of Crohn's disease. We also assessed the combination of anti-OX40L and anti-TNF-alpha MAbs to improve the therapeutic effect. Administration of anti-OX40L MAb markedly ameliorated the clinical and histopathological disease in preventive and therapeutic protocols. In vivo treatment with anti-OX40L MAb decreased CD4(+) T cell infiltration in the colon and suppressed IFN-gamma, IL-2, and TNF-alpha production by lamina propria CD4(+) T cells. The combination with anti-TNF-alpha MAb further improved the therapeutic effect by abolishing IFN-gamma, IL-2, and TNF-alpha production by lamina propria CD4(+) T cells. Our present results suggested a pivotal role of OX40/OX40L in the pathogenesis of T cell-mediated chronic colitis. The OX40L blockade, especially in combination with the TNF-alpha blockade, may be a promising strategy for therapeutic intervention of Crohn's disease.

Animals↗

PubMed2004

The role of intrahepatic CD8+ T cell trapping and NK1.1+ cells in liver-mediated immune regulation.

UNLABELLED: The liver was previously suggested as a site of lymphocyte clearance. Liver-associated lymphocytes that express NK1.1 marker (NKT LAL) play a role in immune modulation. AIM: To determine the role of the liver and of NKT LAL in determining the CD4+/CD8+ balance during tolerance induction. METHODS: Colitis was induced in C57 mice by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Immune tolerance was induced via five oral feedings of colitis-extracted proteins (CEP) from TNBS-colitis colonic wall, starting on the day of colitis induction (group A). Control mice were fed with BSA (group B). To determine the role of NKT cells in immune modulation, NK1.1 depletion was performed in nonfed (group C) and fed (group D) mice. To further evaluate the role of NKT cells in this model, mice in group E were tolerized following NKT depletion. To determine the effect of NKT depletion in a tolerized environment, tolerized mice in group F were NKT depleted following tolerance induction. Peripheral and intrahepatic NK1.1+ and CD4+/CD8+ T cells were determined in all groups. Colitis was assessed by standard clinical and histologic scores. Serum cytokines levels were measured by ELISA. RESULTS: Oral tolerance induction led to a marked alleviation of colitis as manifested by a significant improvement of the clinical, macroscopic, and microscopic scores of colitis (group A vs. group B). NK1.1+ depletion without tolerance induction had a favorable effect on colitis (C). Depletion of NKT LAL prevented the ability to induce tolerance (group D). However, induction of tolerance following NK1.1+ depletion, and NK1.1+ depletion following tolerance induction led to a marked improvement of colitis (groups E and F). Tolerance induction led to a significant increase in NKT LAL numbers. The peripheral CD4+/CD8+ ratio increased up to 3-fold in tolerized vs. non-tolerized mice. A similar increase was observed in NKT-depleted healthy mice in groups C, E, and F (P < 0.005). In contrast, NK1.1+ depletion in the presence of antigen in the bowel led to a reverse effect with a significant decrease in the peripheral CD4+/CD8+ ratio. An opposite effect was observed in the intrahepatic CD4+/CD8+. The peripheral/intrahepatic CD4+/CD8+ ratio increased significantly in tolerized and in healthy mice (A, D, E, F, P < 0.005). In contrast, NK1.1+ depleted fed mice in group C manifested a marked decrease in the peripheral/intrahepatic CD4+/CD8+ ratio. Induction of tolerance led to a marked increase in the IL-10/interferon gamma (IFNgamma) and IL-4/IFNgamma ratios. CONCLUSIONS: In the experimental colitis model, the liver is an important site for CD8+ accumulation during tolerance induction in a process that is independent of NK1.1+ cells. NK1.1+ cells play a dual role in the pro/anti-inflammatory balance. In the presence of antigen, these lymphocytes may be accountable for keeping an anti-inflammatory lymphocyte balance. However, in the absence of antigen, they may induce a pro-inflammatory shift.

Animals↗

PubMed2000

An increased number of CD40-high monocytes in patients with Crohn's disease.

OBJECTIVE: CD40-CD40 ligand (CD40L) interaction is essential for the T-lymphocyte-dependent immune response. This interaction may be operational in the pathogenesis of inflammatory bowel diseases (IBD). The present study examined the expression of CD40 in peripheral blood mononuclear cells (PBMNCs) and tissue specimens, and CD40-stimulated interleukin (IL)-12 release from PBMNCs in IBD. METHODS: The expression of CD40 in PBMNCs and tissue inflammatory cells was examined by flowcytometry and immunohistochemistry, respectively. IL-12 release was measured in cultured media of PBMNCs by an enzyme-linked immunosorbent assay. RESULTS: Most peripheral blood B-lymphocytes expressed CD40 in all subjects. However, in ulcerative colitis (UC) patients, a significantly increased mean fluorescence intensity (MFI) of CD40 on B-lymphocytes was detected, compared with control subjects and patients with Crohn's disease (CD). In contrast, both the percentage positivity and MFI of CD40 on monocytes of active CD subjects were significantly increased, compared with the other groups. In active CD patients, a high level of IL-12 release from PBMNCs was observed by CD40 stimulation, compared with those of the other groups. When primed with IFN-gamma, PBMNCs from inactive CD patients released a significantly high level of IL-12, probably via stimulation by the CD40 monoclonal antibody. In the affected mucosa of CD, numerous CD40-positive cells were demonstrated, and they were also CD68-positive, suggesting these double CD40/ CD68-positive cells are tissue macrophages. CONCLUSIONS: These results suggest that the examination of CD40 expression in PBMNCs might enable the differentiation of CD from UC. CD40-high monocytes in CD patients may play a role in the pathogenesis of CD.

Adolescent↗

PubMedDate not supplied

A new model of chronic colitis in SCID mice induced by adoptive transfer of CD62L+ CD4+ T cells: insights into the regulatory role of interleukin-6 on apoptosis.

OBJECTIVE: The proinflammatory cytokine interleukin (IL)-6 is involved in various chronic inflammatory processes. IL-6 is a predominant cytokine produced by lamina propria T cells in Crohn's disease and experimental colitis. This study was designed to examine the effect of a neutralizing IL-6-receptor (IL-6R) antibody on the programmed cell death of mucosal T cells in the CD62L+ CD4+ SCID transfer model of chronic experimental colitis in mice and to gain more insight into the pathogenesis of this transfer colitis model. METHODS: For adoptive transfer, we isolated CD62L+ CD4+ double-positive T cells from wild-type BALB/c mice followed by intraperitoneal application of 1 million cells in CB17 SCID mice. The purity of the transferred T-cell population was tested by FACS analysis. Cytokine secretion was measured by ELISA. Western blot analysis was performed to detect phospho-STAT-3 in protein extracts of splenic cells. Cryo- and paraffin colon cross-sections were used to perform immunochemical or fluorescence TUNEL stainings. RESULTS: We isolated CD62L+ CD4+ and CD62L- CD4+ T cells. In vitro studies showed an increased production of IL-4 by CD62L- CD4+ T cells compared to CD62L+ T cells. 8-10 weeks after transfer of CD62L+ CD4+ T cells in SCID mice, reconstituted mice developed wasting disease, anal prolapse and diarrhea, whereas mice reconstituted with CD62L- CD4+ did not, similar to anti-IL-6R-treated CD62L+ CD4+-reconstituted SCID mice. Anti-IL-6R-treated reconstituted SCID mice showed decreased levels of activated STAT-3. The previously described efficacy of anti-IL-6R antibody treatment on colitis activity appeared to be due to the induction of apoptosis, as many TUNEL-positive cells were detected in the lamina propria. CONCLUSIONS: These results suggest that the activation of the IL-6/STAT-3-signaling pathway plays a pivotal role in the pathogenesis of CD62L+ CD4+ transfer colitis. Moreover, the application of a neutralizing antibody to IL-6R induces apoptosis in transferred T cells. These data implicate the importance of anti-apoptotic pathways in chronic disease and might contribute to future therapies.

Adoptive Transfer↗

PubMed2002

Interleukin-2-deficient mice develop colitis in the absence of CD28 costimulation.

The intestinal lamina propria contains lymphocytes that are chronically activated by exposure to luminal antigens. Dysregulation of these cells is thought to be central to the pathogenesis of bowel inflammation in experimental models of inflammatory bowel disease. CD28 signals on peripheral T cells provide important costimulatory signals that enhance T-cell proliferation and activation responses to antigens. However, the role of CD28 signals in lamina propria T cells or models of inflammatory bowel disease have not been determined. Accordingly, we examined T lymphocyte activation and proliferation in CD28-deficient (CD28-/-) mice to examine the in vivo roles of CD28 signals in lamina propria T-cell homeostasis. We further generated CD28-/- interleukin (IL)-2-/- double mutant mice to assess the role of CD28 signals in supporting the spontaneously activated and pathogenic T cells that accumulate in IL-2-/- mice. CD28-/- lamina propria T cells displayed reduced activation markers, but were present in normal numbers and proliferated normally. IL-2-/- lymphocytes expressed high levels of bcl-xL, whereas CD28-/- IL-2-/- cells had substantially less bcl-xL. However, lymphadenopathy and ulcerative colitis-like disease occurred in both IL-2-/- and CD28-/- IL-2-/- mice. Thus, CD28 provides a functional costimulatory signal to lamina propria T cells but is not required for homeostasis of these cells. In addition, neither CD28 nor bcl-xL appears to be required for the spontaneous accumulation of T cells in IL-2-/- mice. This suggests that other costimulatory molecules or T-cell receptor ligation alone drive lymphocyte expansion in IL-2-deficient mice.

Animals↗

PubMed1990

Immunohistological studies of surface antigen on colonic lymphoid cells in normal and inflamed mucosa. Comparison of follicular and lamina propria lymphocytes.

Mucosal samples from 16 patients with idiopathic inflammatory bowel disease were examined immunohistologically using several monoclonal antibody combinations, and the results were compared with those obtained in other colonic inflammatory disorders and in normal mucosa. Within and around lymphoid follicles, most T cells expressed the restricted common leucocyte antigen (CD45R, displayed by unprimed T cells). Conversely, most lamina propria T cells were negative for CD45R but stained positively with UCHL1 (a monoclonal antibody recognizing an antigen displayed by primed T lymphocytes). The proportions of T-lymphocyte subpopulations in normal and inflamed mucosa were similar, except that CD6-negative, CD7-positive cells were significantly more frequent in inflammatory bowel disease. A characteristic feature of ulcerative colitis and Crohn's colitis was marked infiltration by CD45R+ lymphoid cells that did not coexpress T- or B-cell surface antigens; some stained positively with plasma cell reagents, suggesting that they may be activated B cells. The observations in the colitis sections are consistent with the interpretation that T and B cells alter their surface antigen expression as they emerge from follicles and enter the inflamed lamina propria.

Antibodies, Monoclonal↗

PubMed2005

T cells that cannot respond to TGF-beta escape control by CD4(+)CD25(+) regulatory T cells.

CD4(+)CD25(+) regulatory T (T reg) cells play a pivotal role in control of the immune response. Transforming growth factor-beta (TGF-beta) has been shown to be required for T reg cell activity; however, precisely how it is involved in the mechanism of suppression is poorly understood. Using the T cell transfer model of colitis, we show here that CD4(+)CD45RB(high) T cells that express a dominant negative TGF-beta receptor type II (dnTbetaRII) and therefore cannot respond to TGF-beta, escape control by T reg cells in vivo. CD4(+)CD25(+) T reg cells from the thymus of dnTbetaRII mice retain the ability to inhibit colitis, suggesting that T cell responsiveness to TGF-beta is not required for the development or peripheral function of thymic-derived T reg cells. In contrast, T reg cell activity among the peripheral dnTbetaRII CD4(+)CD25(+) population is masked by the presence of colitogenic effector cells that cannot be suppressed. Finally, we show that CD4(+)CD25(+) T reg cells develop normally in the absence of TGF-beta1 and retain the ability to suppress colitis in vivo. Importantly, the function of TGF-beta1(-/-) T reg cells was abrogated by anti-TGF-beta monoclonal antibody, indicating that functional TGF-beta can be provided by a non-T reg cell source.

Animals↗

PubMed1992

Phenotypic and functional analysis of lamina propria mononuclear cells from colonoscopic biopsy specimens in patients with ulcerative colitis.

Phenotypic and functional analysis was performed with lamina propria mononuclear cells (LPMCs) isolated from colonoscopic biopsies in 27 patients with ulcerative colitis (UC). The proportion of T lymphocytes displaying HLA-DR antigens, interleukin 2 (IL-2) receptor, and transferrin receptor was greater in active UC than in control diseases. When LPMCs were cultured with IL-2 or phytohemagglutinin for 72 h, there were no significant differences in the proportion of cells bearing these activation markers between active UC and controls. The proportion of CD56+ cells and lymphokine-activated killer (LAK) cell activity was lower in LPMCs from active UC than in control cells, and depletion of CD56+ cells from control lamina propria cells essentially eliminated LAK cell activity. Mucosal T lymphocytes may be activated in vivo during active inflammation in UC, and lower levels of intestinal LAK cell activity may be related to the decrease of CD56+ cells under these conditions.

Adolescent↗