scholarly journals Development of multiple organ-localized autoimmune diseases in nude mice after reconstitution of T cell function by rat fetal thymus graft.

1986 ◽  
Vol 164 (1) ◽  
pp. 60-71 ◽  
Author(s):  
O Taguchi ◽  
T Takahashi ◽  
M Seto ◽  
R Namikawa ◽  
M Matsuyama ◽  
...  
Keyword(s):  
T Cell ◽  
Autoimmune Diseases ◽  
Nude Mice ◽  
Cell Function ◽  
Multiple Organ ◽  
Fetal Thymus ◽  
Cell Functions ◽  
Normal Number ◽  
T Cell Function ◽  
High Incidence

Restoration of T cell function of athymic BALB/c nu/nu mice was investigated after transplantation of xenogeneic thymic rudiments from 15-d-old embryonic rats into kidney subcapsule. The rudiments developed well and formed a proper thymus structure composed of donor epithelia and host lymphocytes. Examination of antibody responses to SRBC revealed that approximately half the normal number of indirect PFCs were observed. Skin grafts from syngeneic BALB/c mice and thymic donor rat strains were accepted, whereas those from allogeneic mice and the rats of other than donor strains were vigorously rejected. Thymus-grafted nude mice under a conventional environment survived without any evident infectious diseases. Histological and immunofluorescence studies, however, showed a high incidence of multiple organ-localized autoimmune diseases in thyroid, salivary gland, stomach, adrenal, prostate, ovary, and testis in mice that produced the corresponding autoantibodies. These results together suggested that rat thymic grafts reconstituted T cell functions of nu/nu mice to a considerable degree, but that organ-localized autoimmune diseases developed, probably because certain auto-antigens of the recipients were recognized by the newly reconstituted host immunity.

scholarly journals Allelic Variation of MHC Structure Alters Peptide Ligands to Induce Atypical Partial Agonistic CD8+ T Cell Function

2003 ◽  
Vol 198 (1) ◽  
pp. 99-109 ◽  
Author(s):  
Dong-Gyun Lim ◽  
Jacqueline M. Slavik ◽  
Katarzyna Bourcier ◽  
Kathrine J. Smith ◽  
David A. Hafler
Keyword(s):  
T Cell ◽  
Intracellular Signaling ◽  
Cell Function ◽  
Peptide Ligands ◽  
T Cell Clones ◽  
Altered Peptide Ligands ◽  
Mhc Molecules ◽  
Cell Functions ◽  
T Cell Function ◽  
Cell Clones

T cell receptors recognize small changes in peptide ligands leading to different T cell responses. Here, we analyzed a panel of HLA-A2–Tax11-19 reactive T cell clones to examine how small allelic variations of MHC molecules could alter the functional outcome of antigen recognition. Similar to the effects induced by antigenic altered peptide ligands, weak or partial agonistic T cell functions were identified in individual T cell clones with the recognition of MHC-altered peptide ligands (MAPLs). Interestingly, one subtype of HLA-A2 molecules induced an unusual type of partial agonistic function; proliferation without cytotoxicity. Modeling of crystallographic data indicated that polymorphic amino acids in the HLA-A2 peptide binding groove, especially the D-pocket, were responsible for this partial agonism. Reciprocal mutations of the Tax peptide side chain engaging the D-pocket indeed restored the agonist functions of the MHC–peptide complex. Whereas early intracellular signaling events were not efficiently induced by these MAPLs, phosphorylated c-Jun slowly accumulated with sustained long-term expression. These data indicate that MAPLs can induce atypical partial agonistic T cell function through structural and biochemical mechanisms similar to altered peptide ligands.

scholarly journals Impaired regulatory T cell function in autoimmune diseases: are microRNAs the culprits?

2015 ◽  
Vol 13 (2) ◽  
pp. 135-137 ◽  
Author(s):  
Varun K Sharma ◽  
Srini V Kaveri ◽  
Jagadeesh Bayry
Keyword(s):  
T Cell ◽  
Autoimmune Diseases ◽  
Regulatory T Cell ◽  
Cell Function ◽  
T Cell Function

scholarly journals Graded Attenuation of TCR Signaling Elicits Distinct Autoimmune Diseases by Altering Thymic T Cell Selection and Regulatory T Cell Function

2010 ◽  
Vol 185 (4) ◽  
pp. 2295-2305 ◽  
Author(s):  
Satoshi Tanaka ◽  
Shinji Maeda ◽  
Motomu Hashimoto ◽  
Chihiro Fujimori ◽  
Yoshinaga Ito ◽  
...  
Keyword(s):  
T Cell ◽  
Autoimmune Diseases ◽  
Regulatory T Cell ◽  
Cell Function ◽  
Cell Selection ◽  
Tcr Signaling ◽  
T Cell Function ◽  
T Cell Selection

scholarly journals Large-Scale Prospective T Cell Function Assays in Shipped, Unfrozen Blood Samples: Experiences from the Multicenter TRIGR Trial

2013 ◽  
Vol 21 (2) ◽  
pp. 203-211 ◽  
Author(s):  
David Hadley ◽  
Roy K. Cheung ◽  
Dorothy J. Becker ◽  
Rose Girgis ◽  
Jerry P. Palmer ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Dependent Diabetes Mellitus ◽  
Biochemical Tests ◽  
Blood Draw ◽  
Blood Samples ◽  
Cell Functions ◽  
Cell Counts ◽  
T Cell Function ◽  
Human T Cell

ABSTRACTBroad consensus assigns T lymphocytes fundamental roles in inflammatory, infectious, and autoimmune diseases. However, clinical investigations have lacked fully characterized and validated procedures, equivalent to those of widely practiced biochemical tests with established clinical roles, for measuring core T cell functions. The Trial to Reduce Insulin-dependent diabetes mellitus in the Genetically at Risk (TRIGR) type 1 diabetes prevention trial used consecutive measurements of T cell proliferative responses in prospectively collected fresh heparinized blood samples shipped by courier within North America. In this article, we report on the quality control implications of this simple and pragmatic shipping practice and the interpretation of positive- and negative-control analytes in our assay. We used polyclonal and postvaccination responses in 4,919 samples to analyze the development of T cell immunocompetence. We have found that the vast majority of the samples were viable up to 3 days from the blood draw, yet meaningful responses were found in a proportion of those with longer travel times. Furthermore, the shipping time of uncooled samples significantly decreased both the viabilities of the samples and the unstimulated cell counts in the viable samples. Also, subject age was significantly associated with the number of unstimulated cells and T cell proliferation to positive activators. Finally, we observed a pattern of statistically significant increases in T cell responses to tetanus toxin around the timing of infant vaccinations. This assay platform and shipping protocol satisfy the criteria for robust and reproducible long-term measurements of human T cell function, comparable to those of established blood biochemical tests. We present a stable technology for prospective disease-relevant T cell analysis in immunological diseases, vaccination medicine, and measurement of herd immunity.

Recombinant CD95-Fc (APG101) prevents graft-versus-host disease in mice without disabling antitumor cytotoxicity and T-cell functions

Blood ◽  
2013 ◽  
Vol 121 (3) ◽  
pp. 556-565 ◽  
Author(s):  
Natalie Hartmann ◽  
Joanna J. Messmann ◽  
Frank Leithäuser ◽  
Maxi Weiswange ◽  
Michael Kluge ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Cell Function ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Host Disease ◽  
Graft Versus Host ◽  
Cell Functions ◽  
T Cell Function

Abstract Graft-versus-host disease (GVHD) induced by transplant-derived T cells represents a major complication after allogeneic bone marrow transplantation (BMT). However, these T cells support engraftment, early T-cell immunity, and mediate the graft-versus-tumor (GVT) effect. Cytotoxic effector functions by transplanted T cells are predominantly mediated by the perforin/granzyme and the CD95/CD95L system. APG101, a novel recombinant human fusion protein consisting of the extracellular domain of CD95 and the Fc domain of an IgG1 antibody inhibited CD95L-induced apoptosis without interfering with T-cell function in vitro and was therefore tested for its ability to prevent GVHD in murine BMT models across minor or major histocompatibility barriers. Starting APG101 treatment either 1 day before or 6 days after transplantation effectively reduced clinical GVHD and rescued survival between 60% and 100% if GVHD was CD95L mediated. APG101 did not interfere with the GVT effect, because P815 mastocytoma and most importantly primary Bcr-Abl–transformed B-cell leukemias were completely eradicated by the alloantigen-specific T cells. Phenotype and homing of alloantigen-specific T cells or their perforin/granzyme-mediated cytotoxicity and proliferative capacity were not affected by APG101 treatment suggesting that APG101 therapy might be useful in GVHD prophylaxis without impairing T-cell function and most importantly preserving GVT activity.

Green tea EGCG, T-cell function, and T-cell-mediated autoimmune encephalomyelitis

2016 ◽  
Vol 64 (8) ◽  
pp. 1213-1219 ◽  
Author(s):  
Dayong Wu
Keyword(s):  
Cell Cycle ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Green Tea ◽  
Cell Function ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Lymphoid Tissues ◽  
Autoimmune Encephalomyelitis ◽  
Cell Functions

Autoimmune diseases are common, disabling immune disorders affecting millions of people. Recent studies indicate that dysregulated balance of different CD4+T-cell subpopulations plays a key role in immune pathogenesis of several major autoimmune diseases. Green tea and its active ingredient, epigallocatechin-3-gallate (EGCG), have been shown to modulate immune cell functions and improve some autoimmune diseases in animal models. In a series of studies we determined EGCG's effect on T-cell functions and its application in autoimmune diseases. We first observed that EGCG inhibited CD4+T-cell expansion induced by polyclonal (mitogens or anti-CD3/CD28) or antigen-specific stimulation. We then showed that EGCG suppressed expansion and cell cycle progression of naïve CD4+T by modulating cell cycle-related proteins. EGCG also inhibited naive CD4+T-cell differentiation into Th1 and Th17 effector subsets by impacting their respective signaling transducers and transcription factors. These results suggest that EGCG may improve T-cell-mediated autoimmune diseases. Using the experimental autoimmune encephalomyelitis (EAE) mice, an animal model for human multiple sclerosis, we found that dietary supplementation with EGCG attenuated the disease's symptoms and pathology. These EGCG-induced changes are associated with findings in the immune and inflammation profiles in lymphoid tissues and the central nervous system: a reduction in proliferation of autoreactive T cells, production of proinflammatory cytokines, and Th1 and Th17 subpopulations, and an increase in regulatory T-cell populations. These results suggest that green tea or its active components may have a preventive and therapeutic potential in dealing with T-cell-mediated autoimmune diseases. However, the translational value of these findings needs to be validated in future human studies.

scholarly journals Blocking effect of lyt-2 antibodies on T cell functions.

1980 ◽  
Vol 152 (3) ◽  
pp. 674-687 ◽  
Author(s):  
N Hollander ◽  
E Pillemer ◽  
I L Weissman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mixed Lymphocyte Reaction ◽  
Cell Function ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Target Cells ◽  
Cell Functions ◽  
T Cell Function ◽  
Helper Function

Monoclonal anti-Lyt-2 antibodies blocked effector function of cytotoxic thymus-derived (T) cells in the absence of added complement. Cytolysis of both allogeneic cells and syngeneic lymphoma or sarcoma target cells was inhibited at the level of the effector lymphocytes. Anti-Lyt-1 and anti-Thy-1 antibodies did not block killer cells. Proliferation of T cells in mixed lymphocyte culture was also inhibited by anti-Lyt-2, but not affected by anti-Lyt-1 or anti-Thy-1 antibodies. Although Lyt-1+ lymphocytes were required in the mixed lymphocyte reaction as helper cells for proliferation of Lyt-2+ lymphocytes, their helper function was not affected by the presence of Lyt-1 antibodies. Thus, although anti-Lyt-1, anti-Lyt-2 and anti-Thy-1 were of the same gamma 2A immunoglobulin class, had high titers, and interacted with T cells to the same extent, only anti-Lyt-2 blocked T cell functions. Polyclonal activation of T lymphocytes by concanavalin A, in contrast to activation by alloantigens, was not inhibited by Lyt-2 antibodies, suggesting that Lyt-2 antibodies interfere with T cell function at the level of the T cell antigen-receptor. The role which Lyt-2 molecules may play in T cell function is discussed.

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