scholarly journals Lessons in IBD Pathogenesis from New Animal Models of Spontaneous Colitis

1995 ◽  
Vol 9 (6) ◽  
pp. 309-315 ◽  
Author(s):  
R Balfour Sartor
Keyword(s):  
T Cell ◽  
B Cells ◽  
Animal Models ◽  
Transforming Growth Factor ◽  
Intestinal Inflammation ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Hla B27 ◽  
Transgenic Rats ◽  
Chronic Intestinal Inflammation

The recent explosion of transgenic and targeted gene deleted (knockout [KO]) rodents has yielded a number of new animal models of spontaneous, chronic intestinal inflammation that have provided novel insights into the pathogenesis of human inflammatory bowel disease (IBD). Spontaneous colitis resulting from deletion of genes encoding key immunoregulatory cytokines (interleukin [IL]-2, IL-10 and transforming growth factor [TGF]-beta) and T cell receptors (TCRs) demonstrates that an intact mucosal immune response prevents colitis. The TCR KO model incriminates B lymphocytes in spontaneous colonic inflammation – TCR KO with intact B cells causes colitis, but simultaneous deletion of T and B cells does not. This model and induction of colitis in severe combined immunodeficient (SCID) mice by constitution with one T cell subset (CD45RHhi), but prevention by addition of the CD45RBlosubset, strongly suggest that T cell subsets down-regulate inflammation in the normal, immunocompetent host. An essential role for normal luminal bacteria in induction and perpetuation of enterocolitis is provided by the absence of chronic intestinal inflammation in germ-free (sterile) IL-2 KO mice and human leukocyte antigen (HLA)-B27 transgenic rats, and attenuated inflammation in IL-2 and IL-10 KO mice raised under specific pathogen-free conditions. The fundamental role of host genetic susceptibility in chronic intestinal inflammation and systemic manifestations is established by development of spontaneous colitis and perianal inflammation in C3H/HeJ Bir substrain mice and HLA-B27 transgenic rats.

scholarly journals Smad7 and Colorectal Carcinogenesis: A Double-Edged Sword

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 612 ◽  
Author(s):  
Edoardo Troncone ◽  
Giovanni Monteleone
Keyword(s):  
Immune Cells ◽  
Transforming Growth Factor ◽  
Intestinal Inflammation ◽  
Association Studies ◽  
Cell Subset ◽  
Colorectal Carcinogenesis ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Chronic Intestinal Inflammation

Colorectal carcinogenesis is a complex process in which many immune and non-immune cells and a huge number of mediators are involved. Among these latter factors, Smad7, an inhibitor of the transforming growth factor (TGF)-β1 signaling that has been involved in the amplification of the inflammatory process sustaining chronic intestinal inflammation, is supposed to make a valid contribution to the growth and survival of colorectal cancer (CRC) cells. Smad7 is over-expressed by tumoral cells in both sporadic CRC and colitis-associated CRC, where it sustains neoplastic processes through activation of either TGFβ-dependent or non-dependent pathways. Consistently, genome-wide association studies have identified single nucleotide polymorphisms of the Smad7 gene associated with CRC and shown that either amplification or deletion of the Smad7 gene associates with a poor prognosis or better outcome, respectively. On the other hand, there is evidence that over-expression of Smad7 in immune cells infiltrating the inflamed gut of patients with inflammatory bowel disease can elicit anti-tumor responses, with the down-stream effect of attenuating CRC cell growth. Taken together, these observations suggest a double role of Smad7 in colorectal carcinogenesis, which probably depends on the cell subset and the biological context analyzed. In this review, we summarize the available evidences about the role of Smad7 in both sporadic and colitis-associated CRC.

scholarly journals Inulin and fructo-oligosaccharides have divergent effects on colitis and commensal microbiota in HLA-B27 transgenic rats

2012 ◽  
Vol 108 (9) ◽  
pp. 1633-1643 ◽  
Author(s):  
Petya T. Koleva ◽  
Rosica S. Valcheva ◽  
Xu Sun ◽  
Michael G. Gänzle ◽  
Levinus A. Dieleman
Keyword(s):  
Intestinal Microbiota ◽  
Intestinal Inflammation ◽  
Denaturing Gradient Gel Electrophoresis ◽  
Control Diet ◽  
Toxin Gene ◽  
Hla B27 ◽  
Transgenic Rats ◽  
Gene Copies ◽  
Chronic Intestinal Inflammation ◽  
Total Bacteria

Modulation of intestinal microbiota by non-digestible carbohydrates may reduce inflammation in inflammatory bowel disease (IBD). The aim of the present study was to assess the effects of inulin and fructo-oligosaccharides (FOS) on intestinal microbiota and colitis in HLA-B27 transgenic rats, a well-validated rodent model for IBD. In this study, 4-week-old rats were fed 8 g/kg body weight inulin or FOS for 12 weeks, or not. Faeces were collected at 4 and 16 weeks of age; and caecal samples were collected at necropsy. The effects of inulin and FOS on chronic intestinal inflammation were assessed using a gross gut score, histology score and levels of mucosal IL-1β. Intestinal microbiota were characterised by quantitative PCR and denaturing gradient gel electrophoresis. Colitis was significantly reduced in all FOS-fed rats compared to the control diet, whereas inulin decreased chronic intestinal inflammation in only half the number of animals. Quantitative analysis of caecal microbiota demonstrated that inulin increased the numbers of total bacteria and theBacteroides-Prevotella-Porphyromonasgroup, FOS increased bifidobacteria, and both fructans decreasedClostridiumcluster XI. In the faecal samples, both inulin and FOS decreased total bacteria,Bacteroides-Prevotella-Porphyromonasgroup, andClostridiumclusters XI and XIVa. FOS increasedBifidobacteriumspp., and mediated a decrease of gene copies of Enterobacteriaceae andClostridium difficiletoxin B in faeces. SCFA concentrations in the faecal and caecal samples were unaffected by the diets. In conclusion, FOS increased the abundance ofBifidobacteriumspp., whereas both fructans reducedClostridiumcluster XI andC. difficiletoxin gene expression, correlating with a reduction of chronic intestinal inflammation.

scholarly journals Alterations of Specific Lymphocytic Subsets with Aging and Age-Related Metabolic and Cardiovascular Diseases

Life ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 246
Author(s):  
Ying Jen Chen ◽  
Yi Jen Liao ◽  
Van Thi Ngoc Tram ◽  
Chung Hao Lin ◽  
Kuo Chen Liao ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cardiovascular Diseases ◽  
Transforming Growth Factor ◽  
Metabolic Diseases ◽  
Replicative Senescence ◽  
Cell Subset ◽  
Serum Levels ◽  
T Cell Subsets ◽  
Age Related

To investigate the association of immunosenescence with aged-related morbidity in the elderly, a clinical study was conducted to analyze and compare the alterations in peripheral blood (PB) T-cell subsets among young healthy (YH) controls, elderly healthy (EH) controls, and age-matched elderly patients with metabolic diseases (E-MDs), with cardiovascular diseases (E-CVDs) or with both (E-MDs/E-CVDs). The frequencies of CD3T, CD8T and invariant natural killer T (iNKT) cells were decreased in the EH, E-MD and E-CVD cohorts, indicating a decline in defense function. Although CD4T and regulatory T (Treg) cell frequencies tended to increase with aging, they were lower in patients with E-MDs and E-CVDs. Subset analyses of T-cells consistently showed the accumulation of senescent T-cell in aging and in patients with E-MDs and E-CVDs, compared with YH volunteers. These accumulated senescent T-cells were undergoing apoptosis upon stimulation due to the replicative senescence stage of T-cells. In addition, serum levels of cytokines, including interferon (IF)-γ, transforming growth factor (TGF)-β and growth differentiation factor (GDF)-15, consistently reflected alterations in T-cell subsets. This study demonstrated that T-cell subset changes with paralleled alterations in cytokines were associated with aging and age-related pathogenesis. These altered T-cell subsets and/or cytokines can potentially serve as biomarkers for the prevention, diagnosis and treatment of age-related morbidities.

scholarly journals T Cell/B Cell Interactions in the Establishment of Protective Immunity

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1074
Author(s):  
Julia Ritzau-Jost ◽  
Andreas Hutloff
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Subset ◽  
Cell Interaction ◽  
T Cell Subsets ◽  
Helper T Cells ◽  
Lymphoid Tissues ◽  
Pathogen Invasion

Follicular helper T cells (Tfh) are the T cell subset providing help to B cells for the generation of high-affinity antibodies and are therefore of key interest for the development of vaccination strategies against infectious diseases. In this review, we will discuss how the generation of Tfh cells and their interaction with B cells in secondary lymphoid organs can be optimized for therapeutic purposes. We will summarize different T cell subsets including Tfh-like peripheral helper T cells (Tph) capable of providing B cell help. In particular, we will highlight the novel concept of T cell/B cell interaction in non-lymphoid tissues as an important element for the generation of protective antibodies directly at the site of pathogen invasion.

Role of CD5 expression on TCRγδ T cell-differentiation and development of chronic intestinal inflammation

2001 ◽  
Vol 120 (5) ◽  
pp. A517-A517
Author(s):  
A MIZOGUCHI ◽  
E MIZOGUCHI ◽  
Y DEJONG ◽  
H TAKEDATSU ◽  
F PREFFER ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Intestinal Inflammation ◽  
T Cell Differentiation ◽  
Chronic Intestinal Inflammation

scholarly journals Long-Term Depletion of Naive T Cells in Patients Treated for Hodgkin's Disease

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3662-3672 ◽  
Author(s):  
Nobukazu Watanabe ◽  
Stephen C. De Rosa ◽  
Anthony Cmelak ◽  
Richard Hoppe ◽  
Leonore A. Herzenberg ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Cell Counts

Abstract We investigated the representation of T cells in patients who had been treated for Hodgkin's disease (HD). We found a marked depletion in both CD4 and CD8 naive T-cell counts that persists up to 30 years after completion of treatment. In contrast, CD4 and CD8 memory T-cell subsets recovered to normal or above normal levels by 5 years posttreatment. Thus, the previously-reported long-term deficit in total CD4 T-cell counts after treatment for HD is due to specific depletion of naive T cells. Similarly, total CD8 T-cell counts return to normal by 5 years only because CD8 memory T cells expand to higher than normal levels. These findings suggest that the treatment (mediastinal irradiation) results in a longterm dysregulation of T-cell subset homeostasis. The profound depletion of naive T cells may explain the altered T-cell function in treated patients, including the poor response to immunization after treatment for HD. Further, in some individuals, we identified expansions of unusual subsets expressing low levels of CD8. Eight-color fluorescence-activated cell sorting analyses showed that these cells largely express CD8αα homodimers and CD57, consistent with the phenotype of potentially extrathymically derived T cells. In addition, these cells, both CD4+ and CD4−, are probably cytotoxic lymphocytes, as they express high levels of intracellular perforin. In adults treated for HD, an increased activity of extrathymic T-cell differentiation may partially compensate for the loss of thymic-derived T cells.

scholarly journals Mechanisms regulating IgA class-specific immunoglobulin production in murine gut-associated lymphoid tissues. II. Terminal differentiation of postswitch sIgA-bearing Peyer's patch B cells.

1983 ◽  
Vol 158 (3) ◽  
pp. 649-669 ◽  
Author(s):  
H Kawanishi ◽  
L Saltzman ◽  
W Strober
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Present Report ◽  
Protein A ◽  
Cell Subset ◽  
Terminal Differentiation ◽  
Lymphoid Tissues ◽  
T Cell Subset ◽  
Iga Production

Our previous studies indicated that cloned T cells obtained from Peyer's patches (PP) (Lyt-1+, 2-, Ia+, and H-2K/D+) evoked immunoglobulin (Ig) class switching of PP B cells from sIgM to sIgA cells in vitro; however, these switch T cells could not in themselves provide optimal help for the differentiation of postswitch sIgA-bearing PP B cells to IgA-secreting cells. Thus, in the present report we described studies focused on mechanisms regulating terminal differentiation of the postswitch PP sIgA-bearing B cells. First, to explore the effect of T cell-derived B cell differentiation factor(s) (BCDF) and macrophage factor(s) (MF) on the terminal maturation of PP B cells, LPS-stimulated PP B cells were co-cultured for 7 d with cloned T cells in the presence or absence of the above factors. In the absence of PP cloned T cells the BCDF and MF had only a modest effect on IgA production, whereas in the presence of PP, but not spleen cloned T cells, IgA production was increased. Next, to investigate the effect of T cells derived from a gut-associated lymphoid tissue (GALT), mesenteric lymph nodes (MLN), as well as from spleen on terminal differentiation of postswitch sIgA PP B cells, LPS-driven PP B cells were precultured with the cloned T cells to induce a switch to sIgA, and subsequently cultured with MLN or spleen T cells or a Lyt-2+-depleted T cell subset in the presence of a T-dependent polyclonal mitogen, staphylococcal protein A. Alternatively, in the second culture period BCDF alone was added, instead of T cells and protein A. Here it was found that B cells pre-exposed to switch T cells from PP, but not spleen, were induced to produce greatly increased amounts of IgA in the presence of protein A and T cells or a Lyt-2+-depleted T cell subset as well as in the presence of BCDF alone. Furthermore, in the presence of BCDF alone many B cells expressed cytoplasmic IgA. These observations strongly support the view that the terminal differentiation of postswitch sIgA B cells is governed by helper T cells and macrophages, or factors derived from such cells. Such cells or factors do not affect preswitch B cells.

Susceptibility of human T cells, T-cell subsets, and B cells to cryopreservation

Cryobiology ◽  
1986 ◽  
Vol 23 (3) ◽  
pp. 199-208 ◽  
Author(s):  
M. Venkataraman ◽  
M.P. Westerman
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
T Cell Subsets ◽  
Human T Cells

scholarly journals Immunoregulation of B lymphocyte colony formation by T cell subsets in patients with chronic lymphocytic leukemia

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 294-298
Author(s):  
LA Fernandez ◽  
JM MacSween ◽  
GR Langley
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Colony Formation ◽  
B Lymphocyte ◽  
Normal Subjects ◽  
Colony Growth ◽  
Lymphocytic Leukemia ◽  
T Cell Subsets ◽  
Cell Colony

Normal B lymphocytes are activated, proliferate, and then differentiate into plasma cells and secrete immunoglobulin (Ig). We have reported that chronic lymphocytic leukemia (CLL) T4 cells help and CLL T8 cells lack suppressor effects on Ig synthesis by normal B cells (Blood 62:767, 1983). We have now explored the earlier phase, proliferation, using B cell colony formation; in semisolid media. B lymphocyte colonies from normal individuals and from patients with CLL were grown in 0.3% agarose overlayed with T cells or T cell subsets and the B cell mitogen staphylococcal protein A. Enriched T cells, OKT4 or OKT8, were obtained either by sheep erythrocyte rosettes or depletion of OKT8 or OKT4 cells by monoclonal antibody or complement, respectively. Twenty thousand B cells from normal subjects yielded 65 +/- 9, 64 +/- 7, and 19 +/- 6 colonies with autologous unfractionated T-, OKT4-, or OKT8- positive cells, respectively. This compared to 29 +/- 11, 81 +/- 11, and 15 +/- 4 colonies from patients with CLL with added autologous unfractionated T-, OKT4-, or OKT8-positive cells. To determine whether the fewer number of colonies in both normal subjects and patients with CLL with OKT8-positive cells was due to suppression or lack of help, the number of OKT4-positive cells was held constant, and OKT8-positive cells were added in increasing numbers. No suppression of colony formation could be demonstrated. Furthermore, the addition of increasing numbers of concanavalin A (Con A)-activated OKT8-positive cells did not suppress colony formation. These results suggest that the CLL T cell subsets behave in a functionally similar manner to normal T cell subsets, namely, (1) that normal and CLL B cell colony growth is helped by OKT4 cells; and (2) in contrast to immunoglobulin secretion by B cells, neither normal nor CLL OKT8 cells, unstimulated or activated by Con A, suppress B cell colony growth.

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