scholarly journals DIFFERENTIATION OF T-CELL PRECURSORS IN NUDE MICE DEMONSTRATED BY IMMUNOFLUORESCENCE OF T-CELL MEMBRANE MARKERS

1973 ◽  
Vol 138 (5) ◽  
pp. 1044-1055 ◽  
Author(s):  
F. Loor ◽  
B. Kindred
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Membrane ◽  
Lymph Nodes ◽  
Nude Mouse ◽  
T Lymphocyte ◽  
Nude Mice ◽  
Cell Functions ◽  
Spleen And Lymph Nodes ◽  
T Cell Membrane

When the thymus from an AKR mouse (TL-, θ-AKR) is grafted to a BALB/c-nu/nu mouse (TL2, θ-C3H), the grafted thymus is rapidly repopulated by host lymphocytes, i.e., lymphocytes having the TL2 and θ-C3H T-lymphocyte membrane antigen markers. θ-C3H lymphocytes also appear rapidly in the spleen and lymph nodes. After a few weeks, BALB/c nude mice grafted with AKR thymus and normal BALB/c mice could not be distinguished on the basis of the number of TL-positive thymocytes or θ-C3H-positive lymphocytes in thymus, spleen, or lymph nodes. These experiments give a definitive proof of the existence of precursor cells for the T compartment of the lymphoid system in the nude mouse. They strongly suggest the involvement of host-derived T cells in the recovery of some T-cell functions by nude mice grafted with allogeneic thymuses.

scholarly journals ACTIVITY OF HOST-DERIVED T CELLS WHICH DIFFERENTIATE IN NUDE MICE GRAFTED WITH CO-ISOGENIC OR ALLOGENEIC THYMUSES

1974 ◽  
Vol 139 (5) ◽  
pp. 1215-1227 ◽  
Author(s):  
Berenice Kindred ◽  
Francis Loor
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Nude Mice ◽  
Precursor Cells ◽  
Donor Strain ◽  
Skin Grafts ◽  
Host Type ◽  
Spleen And Lymph Nodes

If nude mice are grafted with a neonatal thymus, host type precursor cells develop within the graft thymus and after about 6 wk the T-cell population of the thymus, spleen, and lymph nodes is of host type. However, immunological responsiveness produced in nude mice in this manner is incomplete: (a) the ability to react to T-cell mitogens in vitro is greater than in untreated nudes but lower than in normal mice; (b) the response to T-cell dependent antigens is less than normal; and (c) the rejection of skin grafts is slower than in normal animals. Whether host precursor cells which differentiate in an allogeneic thymus are able to reject skin grafts from thymus donor strain appears to depend on the strain combination used.

scholarly journals Protective low avidity anti-tumour CD8+ T cells are selectively attenuated by regulatory T cells

2018 ◽  
Author(s):  
G. Sugiyarto ◽  
D. Prossor ◽  
O. Dadas ◽  
T. Elliott ◽  
E. James
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Lymph Nodes ◽  
Cytotoxic T Lymphocyte ◽  
Tumour Response ◽  
T Cell Responses ◽  
Cell Receptor ◽  
Cell Responses ◽  
Spleen And Lymph Nodes

AbstractRegulatory T cells (Treg) play a major role in the suppression of protective anti-tumour T cell responses. In the CT26 BALB/c murine model of colorectal carcinoma, Tregs differentially suppress responses to two characterised CD8+ T epitopes, AH1 and GSW11, which results in an absence of detectable IFN-γ producing GSW11- specific T cells in the spleen and lymph nodes of tumour challenged mice. Activation of GSW11-specific T cells correlates with protection against tumour growth. Here we show that GSW11-specific T cells are in fact induced in Treg-replete, CT26-bearing mice, where they make up the majority of tumour infiltrating CD8+ lymphocytes, but exhibit a dysfunctional ‘exhausted’ phenotype. This dysfunctional phenotype is induced early in the anti-tumour response in draining lymph nodes, spleens and tumours and is significantly more pronounced in GSW11-specific T cells compared to other tumour-specific T cell responses. Depletion of Tregs prior to tumour challenge significantly reduces the induction of exhaustion in GSW11-specific T cells and correlates with altered T cell receptor (TcR) usage. Moreover, the avidity of GSW11- specific TcRs that expanded in the absence of Tregs was significantly lower compared to TcRs of cytotoxic T lymphocyte (CTL) populations that were diminished in protective anti-tumour responses. This indicates that Tregs suppress the induction of protective anti-tumour T cell responses and may signify that the induction of low avidity T cells, while being more susceptible to exhaustion are the most efficacious in tumour rejection.

scholarly journals Peripheral engraftment of fetal intestine into athymic mice sponsors T cell development: direct evidence for thymopoietic function of murine small intestine.

1992 ◽  
Vol 176 (5) ◽  
pp. 1365-1373 ◽  
Author(s):  
R L Mosley ◽  
J R Klein
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
T Cell Development ◽  
Peripheral T Cells ◽  
Alpha Beta ◽  
Spleen And Lymph Nodes ◽  
Cell Repopulation ◽  
Fetal Intestine

Adult athymic, lethally irradiated, F1-->parent bone marrow-reconstituted (AT x BM) mice were engrafted bilaterally with day 16-18 fetal intestine or fetal thymus into the kidney capsule and were studied for evidence of peripheral T cell repopulation of 1-12 wk postengraftment. Throughout that time period, both types of grafts were macroscopically and histologically characteristic of differentiated thymus or intestine tissues, respectively. Beginning at week 2 postengraftment, clusters of lymphocytes were present within intestine grafts, particularly in subepithelial regions and in areas below villus crypts. As determined by immunofluorescence staining and flow cytometric analyses, lymphocytes from spleen and lymph nodes of sham-engrafted mice (AT x BM-SHAM) were essentially void of T cells, whereas in AT x BM thymus-engrafted (AT x BM-THG) mice, which served as a positive control for T cell repopulation, normal levels of T cells were present in spleen and lymph nodes by week 3 postengraftment, and at times thereafter. Most striking, however, was the finding that T cell repopulation of the spleen and lymph nodes occurred in AT x BM fetal intestine-engrafted (AT x BM-FIG) mice beginning 3 wk postengraftment. Based on H-2 expression, peripheral T cells in AT x BM-FIG mice were of donor bone marrow origin, and consisted of CD3+, T cell receptor (TCR)-alpha/beta+ T cells with both CD4+8- and CD4-8+ subsets. Peripheral T cells in AT x BM-FIG mice were functionally mature, as demonstrated by their capacity to proliferate after stimulation of CD3 epsilon. Moreover, alloreactive cytotoxic T lymphocytes were generated in primary in vitro cultures of spleen cells from AT x BM-FIG and AT x BM-THG mice, though not in spleen cell cultures from AT x BM-SHAM mice. Histologic studies of engrafted tissues 3-4 wk postengraftment demonstrated that thymus leukemia (Tl) antigens were expressed on epithelial surfaces of intestine grafts, and that both TCR-alpha/beta+ and TCR-gamma/delta+ lymphocytes were present in intestine grafts. Collectively, these findings indicate that the murine small intestine has the capacity to initiate and regulate T cell development from bone marrow precursors, thus providing a mechanism by which extrathymic development of intestine lymphocytes occur.

scholarly journals PI3K in T Cell Adhesion and Trafficking

2021 ◽  
Vol 12 ◽  
Author(s):  
Kristoffer H. Johansen ◽  
Dominic P. Golec ◽  
Julie H. Thomsen ◽  
Pamela L. Schwartzberg ◽  
Klaus Okkenhaug
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Mouse Models ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Cell Trafficking ◽  
High Endothelial Venules ◽  
Cell Functions ◽  
And Function

PI3K signalling is required for activation, differentiation, and trafficking of T cells. PI3Kδ, the dominant PI3K isoform in T cells, has been extensively characterised using PI3Kδ mutant mouse models and PI3K inhibitors. Furthermore, characterisation of patients with Activated PI3K Delta Syndrome (APDS) and mouse models with hyperactive PI3Kδ have shed light on how increased PI3Kδ activity affects T cell functions. An important function of PI3Kδ is that it acts downstream of TCR stimulation to activate the major T cell integrin, LFA-1, which controls transendothelial migration of T cells as well as their interaction with antigen-presenting cells. PI3Kδ also suppresses the cell surface expression of CD62L and CCR7 which controls the migration of T cells across high endothelial venules in the lymph nodes and S1PR1 which controls lymph node egress. Therefore, PI3Kδ can control both entry and exit of T cells from lymph nodes as well as the recruitment to and retention of T cells within inflamed tissues. This review will focus on the regulation of adhesion receptors by PI3Kδ and how this contributes to T cell trafficking and localisation. These findings are relevant for our understanding of how PI3Kδ inhibitors may affect T cell redistribution and function.

scholarly journals Different TCR-induced T lymphocyte responses are potentiated by stiffness with variable sensitivity

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Michael Saitakis ◽  
Stéphanie Dogniaux ◽  
Christel Goudot ◽  
Nathalie Bufi ◽  
Sophie Asnacios ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
T Cell ◽  
T Lymphocyte ◽  
Cytokine Production ◽  
Morphological Changes ◽  
The Body ◽  
Lymphocyte Migration ◽  
Cell Functions ◽  
Wide Range

T cells are mechanosensitive but the effect of stiffness on their functions is still debated. We characterize herein how human primary CD4+ T cell functions are affected by stiffness within the physiological Young’s modulus range of 0.5 kPa to 100 kPa. Stiffness modulates T lymphocyte migration and morphological changes induced by TCR/CD3 triggering. Stiffness also increases TCR-induced immune system, metabolism and cell-cycle-related genes. Yet, upon TCR/CD3 stimulation, while cytokine production increases within a wide range of stiffness, from hundreds of Pa to hundreds of kPa, T cell metabolic properties and cell cycle progression are only increased by the highest stiffness tested (100 kPa). Finally, mechanical properties of adherent antigen-presenting cells modulate cytokine production by T cells. Together, these results reveal that T cells discriminate between the wide range of stiffness values found in the body and adapt their responses accordingly.

scholarly journals Induction and abrogation of unresponsiveness in nude mouse cells.

1976 ◽  
Vol 144 (6) ◽  
pp. 1458-1464 ◽  
Author(s):  
R Bösing-Schneider ◽  
M Haug
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nude Mouse ◽  
Nude Mice ◽  
In Vitro Cultures ◽  
Spleen Cells ◽  
Mouse Cells ◽  
In Vivo Administration

Nude mice were injected with antigen and T cells at different times to induce unresponsiveness to SRBC. Spleen cells derived from these mice were tested in vitro for the capability to produce antibody-forming cells against sheep erythrocytes in the presence of a T-cell-replacing factor. It was found that priming with antigen alone did not result in paralysis but a later injection of thymus-derived lymphocytes together with antigen results in unresponsiveness of these cells in vitro, provided there was an interval of several days between the in vivo administration of thymus lymphocytes and the explantations of cells to in vitro cultures.

scholarly journals Generation and selective isolation of IgG antibodies against Jurkat T-cell membrane proteins

2016 ◽  
Vol 19 (1) ◽  
pp. 26-35
Author(s):  
Thuong Minh Trinh ◽  
Mai Thi Xuan Huynh ◽  
Hieu Van Tran
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Membrane ◽  
Polyclonal Antibodies ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Major Barrier ◽  
Hematopoietic Stem ◽  
Jurkat T Cell ◽  
T Cell Membrane

Currently, Graft-versus-Host Disease (GvHD) has been the major barrier to the application of allogeneic bone marrow transplantation for hematopoietic disorders treatment, especially leukemia. GvHD is caused by donor mature T cells’ attack on recipient’s tissues and organs. Recently, T cell depletion using immunomagnetic nanoparticles is one of the most effective methods to prevent GvHD. In this present study, polyclonal antibodies against Jurkat T cell membrane were generated as a component of immunomagnetic particle. Firstly, Jurkat T cell membrane was fractionated by cloud point extraction using Triton X-114. Subsequently, the fractionated membrane was used to subcutaneously immunize rabbits for polyclonal antibodies production with a dose of 50 μg for priming and 25 μg for the next four boostings. Rabbit serum was collected and partially precipitated in 50 percent of saturated ammonium sulfate solution. Next, precipitated polyclonal antibodies were purified by using protein-A affinity chromatography column and the purity was determimed by SDS-PAGE. Afterwards, the purified antibodies were used in immune-fluorescent stainings and the recognition to Jurkat T cells was evaluated via fluorescent microscopic imaging. Finally, the purified antibodies were negatively selected by incubating with TF-1 cell, a hematopoietic stem cell, to eliminate cross-reacting antibodies. The immunocytofluorescent staining results showed that the purified and selected polyclonal antibodies weakly cross-reacted with TF-1 cells and strongly bound to Jurkat T cell

scholarly journals Migration patterns of dendritic cells in the mouse. Traffic from the blood, and T cell-dependent and -independent entry to lymphoid tissues.

1988 ◽  
Vol 167 (2) ◽  
pp. 632-645 ◽  
Author(s):  
J W Kupiec-Weglinski ◽  
J M Austyn ◽  
P J Morris
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Lymph Nodes ◽  
Nude Mice ◽  
Specific Activity ◽  
Lymphoid Tissues ◽  
Migration Patterns ◽  
Peripheral Lymph ◽  
Accessory Cells ◽  
Spleen And Lymph Nodes

Dendritic cells (DC) are critical accessory cells for primary immune responses and they may be important stimulators of transplantation reactions, but little is known of their traffic into the tissues. We have studied the migration of purified splenic DC and T lymphocytes, labeled with 111Indium-tropolone, in syngeneic and allogeneic mice. First we demonstrate that DC can migrate from the blood into some lymphoid and nonlymphoid tissues. Immediately after intravenous administration, radio-labeled DC were sequestered in the lungs, but they actively migrated into the liver and spleen and reached equilibrium levels between 3 and 24 h after transfer. At least half of the radiolabel accumulated in the liver, but the spleen was the principal site of DC localization in terms of specific activity (radiolabel per weight of tissue). DC were unable to enter Peyer's patches, or mesenteric and other peripheral lymph nodes from the bloodstream. This was also true in splenectomized recipients, where the otherwise spleen-seeking DC were quantitatively diverted to the liver. In contrast, T cells homed readily to the spleen and lymph nodes of normal mice and increased numbers were present in these tissues in splenectomized mice. Thus, unlike T cells, DC cannot recirculate from blood to lymph via the nodes. We then show that migration of DC from the blood into the spleen is dependent on the presence of T cells: DC did not enter the spleens of nude mice, but when they were reconstituted with T cells the numbers entering the spleen resembled those in euthymic mice. In nude mice, as in splenectomized recipients, the DC that would normally enter the spleen were quantitatively diverted to the liver. These findings suggest that there is a spleen-liver equilibrium for DC, that may be akin to that existing between spleen and lymph node for T cells. Finally, we followed the traffic of radiolabeled DC via the afferent lymphatics after subcutaneous footpad inoculation. DC accumulated in the popliteal nodes but did not migrate further to the inguinal nodes. There was no difference between euthymic and nude mice, showing that unlike traffic to the spleen, this route probably does not require T cells. These migration patterns were not affected by major histocompatibility barriers, and were only seen with viable, but not glutaraldehyde-fixed, DC.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Absence of the Lyt-2-,L3T4+ lineage of T cells in mice treated neonatally with anti-I-A correlates with absence of intrathymic I-A-bearing antigen-presenting cell function.

1985 ◽  
Vol 161 (5) ◽  
pp. 1029-1047 ◽  
Author(s):  
A M Kruisbeek ◽  
J J Mond ◽  
B J Fowlkes ◽  
J A Carmen ◽  
S Bridges ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocyte ◽  
Cell Function ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 2 ◽  
Class Ii ◽  
Antibody Treatment ◽  
Cell Functions ◽  
Antigen Presenting

In an effort to elucidate the role of intrathymic Ia-bearing antigen-presenting cells (APC) on the development of the class II-restricted T cell repertoire, we examined the effect of neonatal anti-I-A treatment on both intrathymic and splenic APC function; on the generation of Lyt-2-,L3T4+, Lyt-2+,L3T4-, and Lyt-2+,L3T4+ T cells; and on the development of class I- and class II-specific T cell functions. Both the thymus and the spleen are completely devoid of Lyt-2-,L3T4+ T cells in young mice treated from birth with anti-I-A, and also lack functions associated with this subset, i.e., alloantigen-specific interleukin 2 production (present report), allo-class II-specific and self-class II-restricted T cell proliferative responses, and helper cell function for the generation of cytotoxic T lymphocyte responses (18). Development of the Lyt-2+,L3T4- subset proceeds undisturbed in these mice, in accord with the previously reported normal levels of cytotoxic T lymphocyte precursors (18). The thymus contains normal numbers of the immature cortical Lyt-2+,L3T4+ cells, indicating that acquisition of the L3T4 marker, in and of itself, is not influenced by anti-I-A treatment. This striking absence of the lineage of T cells responsible for class II-specific T cell functions is correlated with absence of thymic APC function for class II-restricted T cell clones. When anti-I-A-treated mice are allowed to recover from the antibody treatment, splenic and thymic APC function return to normal in 2-3 wk, and thymic Lyt-2-,L3T4+ T cell numbers and functions reappear before such cells are detectable in the spleen. Collectively, these findings suggest that development of the Lyt-2-,L3T4+ lineage of class II-specific T cells is entirely dependent on functional I-A-bearing APC cells in the thymus. In addition, the presence of normal levels of Lyt-2+,L3T4-T cells argues that generation of the two major subsets of T cells (i.e., Lyt-2+,L3T4- and Lyt-2-,L3T4+) occurs through separate events, involving unique sites of interactions between precursor T cells and nonlymphoid major histocompatibility complex-bearing thymus cells.

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