Induction of Intestinal Inflammation by Adoptive Transfer of CBir1 TCR Transgenic CD4+ T Cells to Immunodeficient Mice

10.3791/63293 ◽  
2021 ◽  
Author(s):  
Wenjing Yang ◽  
Tianming Yu ◽  
Yingzi Cong
Keyword(s):  
T Cells ◽  
Adoptive Transfer ◽  
Intestinal Inflammation ◽  
Immunodeficient Mice

II. The yin and yang of T cells in intestinal inflammation: pathogenic and protective roles in a mouse colitis model

1999 ◽  
Vol 276 (6) ◽  
pp. G1317-G1321 ◽  
Author(s):  
Hilde de Winter ◽  
Hilde Cheroutre ◽  
Mitchell Kronenberg
Keyword(s):  
T Cells ◽  
Adoptive Transfer ◽  
Intestinal Inflammation ◽  
Mucosal Inflammation ◽  
Transfer Model ◽  
Activation Markers ◽  
Immune Disorder ◽  
Immunodeficient Mice ◽  
Yin And Yang ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a multifactorial immune disorder of uncertain etiology. The advent of several mouse models of mucosal inflammation that resemble IBD has provided insight into the mechanisms governing both normal and pathological mucosal immune function. In a widely used adoptive transfer model, the injection into immunodeficient mice of a subset of CD4+T lymphocytes, the CD4+CD45RBhighcells, leads to inflammation of the intestine. Pathogenesis is due in part to the secretion of proinflammatory cytokines. The induction of colitis can be prevented by cotransfer of another CD4+subpopulation, the CD4+CD45RBlowT cells. This population behaves analogously to the CD4+CD45RBhighpopulation in terms of the acquisition of activation markers and homing to the host intestine. However, their lymphokine profile when activated is different, and anti-inflammatory cytokines secreted and/or induced by CD4+CD45RBlowT cells prevent colitis. In this themes article, a description of the adoptive transfer model is given, the factors that promote and prevent colitis pathogenesis are discussed, and some controversial aspects of the model are addressed.

scholarly journals Aberrant regulation of superantigen responses during T-cell reconstitution and graft-versus-host disease in immunodeficient mice

Blood ◽  
2002 ◽  
Vol 100 (6) ◽  
pp. 2216-2224
Author(s):  
David Spaner ◽  
Xiaofang Sheng-Tanner ◽  
Andre C. Schuh
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Adoptive Transfer ◽  
Scid Mice ◽  
Control Mechanisms ◽  
Activated T Cells ◽  
Host Disease ◽  
Immunodeficient Mice ◽  
Graft Versus Host

Acute graft-versus-host disease (GVHD) after allogeneic stem cell transplantation is associated with impaired deletion and anergy of host-reactive T cells. To elucidate the immunoregulatory events that may contribute to such dysregulated T-cell responses in GVHD, we studied superantigen (SAg) responses after adoptive T-cell transfer into severe combined immunodeficient (SCID) mice. SAg responses are normally regulated by mechanisms involving deletion and anergy, with SAg-reactive T cells typically being deleted rapidly in vivo. In a SCID mouse model of GVHD, however, allogeneic host SAg-reactive T cells were not deleted rapidly, but rather persisted in increased numbers for several months. Moreover, depending on the timing of SAg stimulation and the numbers of T cells transferred, dysregulation (impaired deletion and anergy) of SAg responses could be demonstrated following the adoptive transfer of syngeneic T cells into SCID mice as well. Transgenic T-cell receptor-bearing KJ1-26.1+ T cells were then used to determine the fate of weakly reactive T cells after adoptive transfer and SAg stimulation. When transferred alone, KJ1-26.1+ T cells demonstrated impaired deletion and anergy. In the presence of more strongly staphylococcal enterotoxin B (SEB)–reactive T cells, however, KJ1-26.1+ T cells were regulated normally, in a manner that could be prevented by inhibiting the effects of more strongly SEB-reactive cells or by increasing the level of activation of the KJ1-26.1+ T cells themselves. We suggest that the control mechanisms that normally regulate strongly activated T cells in immunocompetent animals are lost following adoptive transfer into immunodeficient hosts, and that this impairment contributes to the development of GVHD.

scholarly journals Adoptive transfer of splenic T cells restores the hepatic fibrogenic response to chronic cholestasis in severe combined immunodeficient mice

2006 ◽  
Vol 20 (5) ◽  
Author(s):  
Ian Neil Hines ◽  
Michael Kremer ◽  
Richard Jameson Milton ◽  
Ashley Marie Perry ◽  
April L Black ◽  
...  
Keyword(s):  
T Cells ◽  
Adoptive Transfer ◽  
Immunodeficient Mice ◽  
Chronic Cholestasis

Abstract WP96: The Role of T-Lymphocytes in Neuroregeneration After Cerebral Ischemia

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Kai Diederich ◽  
Antje Schmidt ◽  
Jan-Kolja Strecker ◽  
Wolf-Rüdiger Schäbitz ◽  
Jens Minnerup
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
Adoptive Transfer ◽  
Critical Role ◽  
Chronic Phase ◽  
Cognitive Testing ◽  
Neurological Deficits ◽  
Ischemic Brain ◽  
Immunodeficient Mice

Introduction: Inflammation plays a critical role in the pathogenesis of ischemic stroke. The CNS responds to ischemic injury with an inflammatory process, characterized by an infiltration of inflammatory cells. Particularly T cells exhibit a great impact on early stroke outcome as recent studies showed that ablation of these cells decrease infarct size and improve neurological deficits in the acute phase after stroke. However, the role of T cells in the sub-acute and chronic phase after stroke is unknown. T cells are essential for effective neurogenesis and angiogenesis, mechanisms that are integral for successful regeneration after stroke. We assessed the hypothesis that T cells influence cellular mechanisms of post-ischemic neuroregeneration and consequently affect functional and structural recovery. Methods: 24 wild type (wt) and 11 RAG1 -/- mice were subjected to photothrombotic ischemia, a subset of 12 wt and 6 RAG1 -/- animals underwent training in motorized running wheels starting at day 3 following ischemia until the end of the experiment on day 28. Sensorimotor and cognitive testing was applied to quantify the recovery process. To label newly generated neurons, 5-Chloro-2′-deoxyuridine (CldU) and iododeoxyuridine (IdU) were administered at days 1 and 2 (CldU) and once weekly until day 28 (IdU) after ischemia. In a subsequent experiment, 17 RAG1 -/- mice were subjected to photothrombotic ischemia and underwent training, a subset of 10 animals received an adoptive transfer of T cells. Functional testing and cellular labeling were carried out in analogy to the first experiment. Results: Training improved recovery from sensorimotor and cognitive deficits following cortical ischemia in wt animals and increased the generation of new neurons in the ischemic brain. Rehabilitative training did not induce functional recovery in RAG1 -/- animals and had no effect on the generation of neurons. Adoptive transfer of T cells into the immunodeficient mice restored the ability for regeneration. Conclusion: T cells play an essential role in the functional and structural regeneration following ischemic brain injury. These results provide new clues on the complex mechanism by which immune cells impact different stages of the pathogenesis of ischemic stroke.

scholarly journals T cells, but not B cells, are required for bowel inflammation in interleukin 2-deficient mice.

1995 ◽  
Vol 182 (5) ◽  
pp. 1567-1572 ◽  
Author(s):  
A Ma ◽  
M Datta ◽  
E Margosian ◽  
J Chen ◽  
I Horak
Keyword(s):  
T Cells ◽  
B Cells ◽  
Bowel Disease ◽  
Double Mutant ◽  
Intestinal Inflammation ◽  
Interleukin 2 ◽  
Mutant Mice ◽  
Immunodeficient Mice ◽  
Inflammatory Bowel ◽  
Deficient Mice

Interleukin-2 (IL-2)-deficient (IL-2-/-) mice develop anemia and colonic inflammatory bowel disease. To elucidate the mechanism of this disease, we have bred IL-2-/- mice to two strains of immunodeficient mice, RAG-2-deficient (RAG-2-/-, lacking B and T cells) and JH-deficient mice (JH-/-, lacking B cells). IL-2-/-, RAG-2-/- double-mutant mice are disease free, while IL-2-/-, JH-/- double-mutant mice succumb to bowel disease at the same rate as IL-2-/- littermates. IL-2-/-, JH-/- mice do not, however, succumb to anemia. Thus, spontaneous intestinal inflammation in IL-2-/- mice requires mature T cells, not B cells, while anemia is dependent on B cells.

scholarly journals Aberrant regulation of superantigen responses during T-cell reconstitution and graft-versus-host disease in immunodeficient mice

Blood ◽  
2002 ◽  
Vol 100 (6) ◽  
pp. 2216-2224 ◽  
Author(s):  
David Spaner ◽  
Xiaofang Sheng-Tanner ◽  
Andre C. Schuh
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Adoptive Transfer ◽  
Scid Mice ◽  
Control Mechanisms ◽  
Activated T Cells ◽  
Host Disease ◽  
Immunodeficient Mice ◽  
Graft Versus Host

Abstract Acute graft-versus-host disease (GVHD) after allogeneic stem cell transplantation is associated with impaired deletion and anergy of host-reactive T cells. To elucidate the immunoregulatory events that may contribute to such dysregulated T-cell responses in GVHD, we studied superantigen (SAg) responses after adoptive T-cell transfer into severe combined immunodeficient (SCID) mice. SAg responses are normally regulated by mechanisms involving deletion and anergy, with SAg-reactive T cells typically being deleted rapidly in vivo. In a SCID mouse model of GVHD, however, allogeneic host SAg-reactive T cells were not deleted rapidly, but rather persisted in increased numbers for several months. Moreover, depending on the timing of SAg stimulation and the numbers of T cells transferred, dysregulation (impaired deletion and anergy) of SAg responses could be demonstrated following the adoptive transfer of syngeneic T cells into SCID mice as well. Transgenic T-cell receptor-bearing KJ1-26.1+ T cells were then used to determine the fate of weakly reactive T cells after adoptive transfer and SAg stimulation. When transferred alone, KJ1-26.1+ T cells demonstrated impaired deletion and anergy. In the presence of more strongly staphylococcal enterotoxin B (SEB)–reactive T cells, however, KJ1-26.1+ T cells were regulated normally, in a manner that could be prevented by inhibiting the effects of more strongly SEB-reactive cells or by increasing the level of activation of the KJ1-26.1+ T cells themselves. We suggest that the control mechanisms that normally regulate strongly activated T cells in immunocompetent animals are lost following adoptive transfer into immunodeficient hosts, and that this impairment contributes to the development of GVHD.

scholarly journals An Essential Role for Interleukin 10 in the Function of Regulatory T Cells That Inhibit Intestinal Inflammation

1999 ◽  
Vol 190 (7) ◽  
pp. 995-1004 ◽  
Author(s):  
Chrystelle Asseman ◽  
Smita Mauze ◽  
Michael W. Leach ◽  
Robert L. Coffman ◽  
Fiona Powrie
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cell Population ◽  
Transforming Growth Factor ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Cd4 Cells ◽  
Immunodeficient Mice

A T helper cell type 1–mediated colitis develops in severe combined immunodeficient mice after transfer of CD45RBhigh CD4+ T cells and can be prevented by cotransfer of the CD45RBlow subset. The immune-suppressive activities of the CD45RBlow T cell population can be reversed in vivo by administration of an anti-transforming growth factor β antibody. Here we show that interleukin (IL)-10 is an essential mediator of the regulatory functions of the CD45RBlow population. This population isolated from IL-10–deficient (IL-10−/−) mice was unable to protect from colitis and when transferred alone to immune-deficient recipients induced colitis. Treatment with an anti–murine IL-10 receptor monoclonal antibody abrogated inhibition of colitis mediated by wild-type (WT) CD45RBlow CD4+ cells, suggesting that IL-10 was necessary for the effector function of the regulatory T cell population. Inhibition of colitis by WT regulatory T cells was not dependent on IL-10 production by progeny of the CD45RBhigh CD4+ cells, as CD45RBlow CD4+ cells from WT mice were able to inhibit colitis induced by IL-10−/− CD45RBhigh CD4+ cells. These findings provide the first clear evidence that IL-10 plays a nonredundant role in the functioning of regulatory T cells that control inflammatory responses towards intestinal antigens.

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