scholarly journals SPLENIC REPLENISHMENT OF SYNERGISTIC ABILITY TO BONE MARROW AND THYMIC CELLS OF NEONATALLY SPLENECTOMIZED CBA MICE

1972 ◽  
Vol 136 (4) ◽  
pp. 761-768 ◽  
Author(s):  
R. A. Bucsi ◽  
F. Borek ◽  
J. R. Battisto
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Red Blood Cells ◽  
Cell Population ◽  
Blood Cells ◽  
Spleen Cells ◽  
Cba Mice ◽  
Adult Mice ◽  
Collaborative Capacity

Bone marrow (B) and thymic (T) cells taken from adult mice that had been splenectomized within 24 hr of birth showed an inability to cooperate in the IgM response to sheep red blood cells. The defect in collaborative capacity was apparent in both sets of cells, but appeared to be more pronounced in the T cell population. Splenectomy performed at various neonatal intervals indicated that if removal of the spleen were delayed until 6 days after birth, B and T cells of the adult showed a 60% restoration in cooperation. Replenishment of the synergistic ability after neonatal splenectomy could be achieved by injecting spleen cells immediately after spleen removal or 2 months postsplenectomy.

A comparison of murine T-cell–depleted adult bone marrow and full-term fetal blood cells in hematopoietic engraftment and immune reconstitution

Blood ◽  
2002 ◽  
Vol 99 (1) ◽  
pp. 364-371 ◽  
Author(s):  
Benny J. Chen ◽  
Xiuyu Cui ◽  
Gregory D. Sempowski ◽  
Maria E. Gooding ◽  
Congxiao Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Cord Blood ◽  
Blood Cells ◽  
Immune Reconstitution ◽  
Full Term ◽  
Fetal Blood ◽  
Adult Bone

Umbilical cord blood has been increasingly used as a source of hematopoietic stem cells. A major area of concern for the use of cord blood transplantation is the delay in myeloid and lymphoid recovery. To directly compare myeloid and lymphoid recovery using an animal model of bone marrow and cord blood as sources of stem cells, hematopoietic engraftment and immune recovery were studied following infusion of T-cell–depleted adult bone marrow or full-term fetal blood cells, as a model of cord blood in a murine allogeneic transplantation model (C57BL/6 [H-2b] → BALB/c [H-2d]). Allogeneic full-term fetal blood has poorer radioprotective capacity but greater long-term engraftment potential on a cell-to-cell basis compared with T-cell–depleted bone marrow. Allogeneic full-term fetal blood recipients had decreased absolute numbers of T, B, and dendritic cells compared with bone marrow recipients. Splenic T cells in allogeneic full-term fetal blood recipients proliferated poorly, were unable to generate cytotoxic effectors against third-party alloantigens in vitro, and failed to generate alloantigen-specific cytotoxic antibodies in vivo. In addition, reconstituting T cells in fetal blood recipients had decreased mouse T-cell receptorδ single-joint excision circles compared with bone marrow recipients. At a per-cell level, B cells from fetal blood recipients did not proliferate as well as those found in bone marrow recipients. These results suggest that full-term fetal blood can engraft allogeneic hosts across the major histocompatibility barrier with slower hematopoietic engraftment and impaired immune reconstitution.

scholarly journals Regression and inhibition of sarcoma growth by interference with a radiosensitive T-cell population.

1978 ◽  
Vol 148 (3) ◽  
pp. 799-804 ◽  
Author(s):  
K E Hellström ◽  
I Hellström ◽  
J A Kant ◽  
J D Tamerius
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Cell Population ◽  
Whole Body ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Irradiation Irradiation

BALB/c mice were inoculated subcutaneously with 10(6) cells from either of two syngeneic sarcomas 1315 and 1425. 6--8 days later, the mice were randomized into groups which were left untreated or given 400 rads of whole body irradiation. Irradiation significantly retarded the growth of both sarcomas, and complete regressions were seen of approximately equal to 30% of the small, established 1315 tumors. The anti-tumor effect of irradiation was abolished if the irradiated mice were inoculated with a T-cell-enriched (but not with a T-cell deprived) suspension of syngeneic spleen cells, suggesting that the irradiation inhibited tumor growth by affecting a radiosensitive population of host suppressor T cells.

Abnormal Distribution of Erythroid Progenitors Populations in Mice Lacking p45 NF-E2.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1988-1988
Author(s):  
Jadwiga Gasiorek ◽  
Gregory Chevillard ◽  
Zaynab Nouhi ◽  
Volker Blank
Keyword(s):  
Bone Marrow ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Conflicts Of Interest ◽  
Globin Genes ◽  
Erythroid Progenitors ◽  
Erythroid Progenitor ◽  
Adult Mice ◽  
Deficient Mice

Abstract Abstract 1988 Poster Board I-1010 The NF-E2 transcription factor is a heterodimer composed of a large hematopoietic-specific subunit called p45 and widely expressed 18 to 20-kDa small Maf subunits. In MEL (mouse erythroleukemia) cells, a model of erythroid differentiatin, the absence of p45 is inhibiting chemically induced differentiation, including induction of globin genes. In vivo, p45 knockout mice were reported to show splenomegaly, severe thrompocytopenia and mild erythroid abnormalities. Most of the mice die shortly after birth due to haemorrhages. The animals that survive display increased bone, especially in bony sites of hematopoiesis. We confirmed that femurs of p45 deficient mice are filled with bone, thus limiting the space for cells. Hence, we observed a decrease in the number of hematopoietic cells in the bone marrow of 3 months old mice. In order to analyze erythroid progenitor populations we performed flow cytometry using the markers Ter119 and CD71. We found that p45 deficient mice have an increased proportion of early erythroid progenitors (proerythroblasts) and a decreased proportion of late stage differentiated red blood cells (orthochromatic erythroblasts and reticulocytes) in the spleen, when compared to wild-type mice. We showed that the liver of p45 knockout adult mice is also becoming a site of red blood cell production. The use of secondary sites, such as the spleen and liver, suggests stress erythropoiesis, likely compensating for the decreased production of red blood cells in bone marrow. In accordance with those observations, we observed about 2 fold increased levels of erythropoietin in the serum of p45 knockout mice.Overall, our data suggest that p45 NF-E2 is required for proper functioning of the erythroid compartment in vivo. Disclosures: No relevant conflicts of interest to declare.

scholarly journals INDUCTION OF A HEMOLYSIN RESPONSE IN VITRO

1970 ◽  
Vol 132 (6) ◽  
pp. 1267-1278 ◽  
Author(s):  
Klaus-Ulrich Hartmann
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
T Cells ◽  
Cell Suspension ◽  
Cell Population ◽  
Cell Suspensions ◽  
Spleen Cells ◽  
Bone Marrow Derived Cells ◽  
Thymus Cells

The immune response to foreign erythrocytes was studied in vitro. Two subpopulations of cells were prepared. One was a population of bone marrow-derived spleen cells, taken from thymectomized, irradiated, and bone marrow-reconstituted mice; there was evidence that most of the precursors of the PFC had been present in this cell population, but few PFC developed in cultures of these cells alone in the presence of immunogenic erythrocytes. Another cell suspension was made from spleens of mice which had been irradiated and injected with thymus cells and erythrocytes; these cells were called educated T cells. The two cell suspensions together allow the formation of PFC in the presence of the erythrocytes which were used to educate the T cells, but not in the presence of noncross-reacting erythrocytes. If bone marrow-derived cells and T cells were kept in culture together with two different species of erythrocytes, and if one of the erythrocytes had been used to educate the T cells, then PFC against each of the erythrocytes could be detected.

scholarly journals Interval of IL-2 Administration Has a Major Impact on Treatment Efficacy for Regulatory T Cell Expansion and Homeostasis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1928-1928
Author(s):  
Yuriko Kishi ◽  
Yusuke Meguri ◽  
Miki Iwamoto ◽  
Takeru Asano ◽  
Takanori Yoshioka ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cell ◽  
Dose Interval ◽  
Daily Administration ◽  
Optimum Dose ◽  
Spleen Cells ◽  
Ki 67 ◽  
Significant Difference

Abstract IL-2 has a critical role in the immune homeostasis by expansion and maintenance of regulatory T cell (Treg). We previously demonstrated that low-dose IL-2 administration preferentially increased Treg in patients with active chronic GVHD and resulted in clinical improvement of the symptoms. In these years, the tolerogenic effects of IL-2 have been tested in the setting of various autoimmune-based diseases by many clinical trials. However, the schedules of IL-2 administration in each trial are different and the optimal strategy for expansion and maintenance of Treg is still unclear. To tackle this issue, we examined the impact of IL-2 dose intervals on Treg and the optimization for the induction and maintenance therapy by using murine IL-2 therapy model. CD4+CD25+Foxp3+ Treg were analyzed comparing with CD4+CD25-Foxp3- conventional CD4 T cells (Tcon) and CD8+ T cells. The expressions of Ki-67 and Bcl-2 in each subset were also examined. First, we performed the experimental allogeneic BMT, in which model 1x10E6 spleen cells (CD45.2) and 5x10E6 T cell depleted bone marrow cells (CD45.1) from C57BL/6 donors were transplanted into lethally-irradiated B6D2F1 recipients (CD45.2). To explore the optimum dose-interval for the increase of Treg from the baseline level as the induction therapy, we administered 5000 IU of IL-2 to recipients subcutaneously once (Induction-A), twice (Induction-B), four (Induction -C) or seven (Induction-D) times a week from day 35 to 49 after transplant. On day 50 after transplant, peripheral blood and spleen cells of mice from each group were harvested and CD45.1+H-2Kd- Donor bone-marrow derived lymphocytes were evaluated. The absolute number and %Treg of CD4 T cells, and the Ki-67 and Bcl-2 expression in Treg were compared with each frequency of administration. To increase Treg from baseline, the daily administration (Induction-D) provided the best Treg response among the tested groups and there was significant difference between control group and group I-D (%Treg: 10.5 % vs. 16.7 %, p<0.05). Treg proliferation was positively related to the frequency of IL-2 administration (%Ki-67+ cells: 17.7%, 17.2 %, vs. 9.9%, 9.0% and 7.8%, respectively, p<0.05). Secondly, we investigated the optimum dose-interval for the maintenance of expanded Treg level after the initial inductive IL-2 administration. We expanded Treg by daily administration of IL-2 to B6 mice for 2 weeks, thereafter we administrated IL-2 twice (Maintenance-A), four (Maintenance-B), or seven (Maintenance-C) times a week from day 14 to 21 for the maintenance. Of interest, to maintain expanded Treg level after the induction IL-2 therapy, Treg in cohorts of Maintenance-B and Maintenance-C were significantly higher than in cohort Maintenance-A (mean 9.7%, 10.2% vs 7.1%, respectively) and there was no significant differences between cohorts Maintenance-B and Maintenance-C, suggesting daily administration is not necessary and intermittent administration within the threshold may work for the maintenance of expanded Treg level after the intensive IL-2 administration. Treg proliferation of cohort Maintenance-C was significantly higher than that of the other cohorts (mean %Ki-67: 19.8 %, 20.5 % vs. 23.9 %, p<0.05). There were no significant difference in Bcl-2 expression in Treg among these cohorts but seemed negatively related to the frequency of IL-2 administration. These data suggested that daily administration of IL-2 seems to be optimal for expansion of Treg for induction therapy. In contrast, to maintain the expanded Treg, daily administration may not be required but less frequent times of administration within the threshold could be preferable. Taken together, the interval of IL-2 administration should be a major factor for Treg homeostasis as well as IL-2 dosage. Our data provide important information for developing therapeutic strategies to modulate Treg homeostasis in vivo and promote immune tolerance after transplant. Disclosures No relevant conflicts of interest to declare.

scholarly journals Bone Marrow-Resident Vδ1 T Cells Co-express TIGIT With PD-1, TIM-3 or CD39 in AML and Myeloma

2021 ◽  
Vol 8 ◽  
Author(s):  
Franziska Brauneck ◽  
Pauline Weimer ◽  
Julian Schulze zur Wiesch ◽  
Katja Weisel ◽  
Lisa Leypoldt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Hematologic Malignancies ◽  
Cell Subpopulation ◽  
Multiparameter Flow Cytometry ◽  
Dependent Manner

Background: γδ T cells represent a unique T cell subpopulation due to their ability to recognize cancer cells in a T cell receptor- (TCR) dependent manner, but also in a non-major histocompatibility complex- (MHC) restricted way via natural killer receptors (NKRs). Endowed with these features, they represent attractive effectors for immuno-therapeutic strategies with a better safety profile and a more favorable anti-tumor efficacy in comparison to conventional αβ T cells. Also, remarkable progress has been achieved re-activating exhausted T lymphocytes with inhibitors of co-regulatory receptors e.g., programmed cell death protein 1 (PD-1), T cell immunoreceptor with Ig and ITIM domains (TIGIT) and of the adenosine pathway (CD39, CD73). Regarding γδ T cells, little evidence is available. This study aimed to immunophenotypically characterize γδ T cells from patients with diagnosed acute myeloid leukemia (AML) in comparison to patients with multiple myeloma (MM) and healthy donors (HD).Methods: The frequency, differentiation, activation, and exhaustion status of bone marrow- (BM) derived γδ T cells from patients with AML (n = 10) and MM (n = 11) were assessed in comparison to corresponding CD4+ and CD8+ T cells and peripheral blood- (PB) derived γδ T cells from HDs (n = 16) using multiparameter flow cytometry.Results: BM-infiltrating Vδ1 T cells showed an increased terminally differentiated cell population (TEMRAs) in AML and MM in comparison to HDs with an aberrant subpopulation of CD27−CD45RA++ cells. TIGIT, PD-1, TIM-3, and CD39 were more frequently expressed by γδ T cells in comparison to the corresponding CD4+ T cell population, with expression levels that were similar to that on CD8+ effector cells in both hematologic malignancies. In comparison to Vδ2 T cells, the increased frequency of PD-1+-, TIGIT+-, TIM-3+, and CD39+ cells was specifically observed on Vδ1 T cells and related to the TEMRA Vδ1 population with a significant co-expression of PD-1 and TIM-3 together with TIGIT.Conclusion: Our results revealed that BM-resident γδ T cells in AML and MM express TIGIT, PD-1, TIM-3 and CD39. As effector population for autologous and allogeneic strategies, inhibition of co-inhibitory receptors on especially Vδ1 γδ T cells may lead to re-invigoration that could further increase their cytotoxic potential.

scholarly journals PHENYTOIN-ASSOCIATED LYMPHOADENOPATHY MIMICKING A PERIPHERAL T-CELL LYMPHOMA

2010 ◽  
Vol 2 (2) ◽  
pp. e2010028 ◽  
Author(s):  
Mark E. Johns ◽  
Lynn C. Moscinski ◽  
Lubomir Sokol
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cervical Lymphadenopathy ◽  
Excisional Biopsy ◽  
Whole Body ◽  
Cervical Lymph Nodes

We report a case of phenytoin-induced pseudolymphoma in a 28-year-old male with a history of autism and seizure disorder.  The patient presented with bilateral cervical lymphadenopathy that was shown to be moderately to markedly FDG-avid on a whole body PET/CT scan.  Flow cytometry analysis of peripheral blood and bone marrow mononuclear cells detected identical T cell population with aberrant immunophenotype.  Additionally, a TCR beta gene was found to be clonally rearranged in both peripheral blood and bone marrow supporting a clonal origin of atypical T cells. However, no such clonal population of T-cells could be detected in a pathologic specimen obtained from an excisional biopsy of one of the patient’s cervical lymph nodes. After discontinuing the patient’s phenytoin, his lymphadenopathy has nearly completely resolved and circulation clonal T cell population disappeared with 12 months of follow-up.

NLRP10-Deficient Mice Reveal a Crucial Role for Dendritic Cell Activity in the Initiation of the Allogeneic Response to Transfused Red Blood Cells

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4113-4113
Author(s):  
Stephanie C. Eisenbarth ◽  
Jeanne E Hendrickson ◽  
Samuele Calabro ◽  
Antonia Gallman
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Red Blood Cells ◽  
T Cell Activation ◽  
Blood Cells ◽  
Cell Activation ◽  
Innate Immune ◽  
Deficient Mice

Abstract The generation of antibodies against transfused red blood cells (RBCs) can pose a serious health risk, especially in chronically transfused patients requiring life-long transfusion support; yet our understanding of what immune signals or cells dictate when someone will become alloimmunized is lacking. Every non-autologous red cell unit has multiple antigens foreign to the transfused recipient; some people respond to these foreign antigens with an adaptive immune response and some do not. Given the now well established role of innate immune signals in regulating adaptive immunity, understanding if and how innate immunity is triggered during transfusion may allow development of therapies to prevent alloimmunization in chronically transfused subjects such as those with myelodysplasia or hemoglobinopathies. We have established a murine model system in which we can evaluate both the role of particular innate immune stimuli as well as particular cells of the immune system in regulating the allogeneic response to transfused red blood cells. A particularly useful transgenic “HOD mouse” has been engineered, which encodes a triple fusion protein and provides a unique tool to directly assess both RBC-specific T and B cell responses. This RBC-specific antigen contains the model protein antigen hen egg lysozyme (HEL) fused to chicken ovalbumin (OVA) fused to the human Duffybblood group antigen (HEL-OVA-Duffy) as an integral membrane protein under control of the beta globin promoter. Transfusion of genetically targeted mice lacking various innate immune receptors allows us to screen for important immune pathways regulating the response to allogeneic RBCs. Using these models, we recently discovered that mice lacking the NOD-like receptor NLRP10 fail to develop alloimmunity to transfused red blood cells. Surprisingly, the early innate immune cytokine response, including IL-6, IL-1beta and TNF-alpha, was unaffected in mice lacking NLRP10. Yet both B cell and T cell activation in the spleen to the transgenic transfused RBCs was abrogated. Inclusion of OVA in the alloantigen of the HOD mice allows us to readily study naïve CD4+ T cell activation following transfusion by using the OTII T cell receptor (TCR) transgenic mice in which essentially all T cells express one antigen receptor specific for a peptide of OVA. By tracking rounds of cell division we found that adoptively transferred OTII undergo more than 5-8 rounds of division in the spleen three days following transfusion of HOD RBCs in WT recipients. In contrast, no OTII proliferation was observed in NLRP10-deficient mice following OTII adoptive transfer and HOD RBC transfusion, suggesting that T cells are failing to receive activation signals by splenic antigen presenting cells. We have previously demonstrated that NLRP10-deficient dendritic cells fail to migrate from peripheral tissues such as the skin to draining lymph nodes. Our preliminary data now suggest that NLRP10-deficient dendritic cells are able to process and present RBC-derived antigens, but do not migrate to T cell zones in the spleen to prime naïve RBC-specific T cells. The relative role of dendritic cells, B cells and macrophages in the induction of erythrocyte alloimmunization remain unclear. Further, the need for DC migration within the spleen in the induction of alloimmunity to transfused RBCs has not been addressed. These mice allow us for the first time to answer these fundamental immunologic questions during transfusion. Future work will aim to determine how dendritic cell movement within the spleen is regulated during transfusion in NLRP10-deficient mice and the specific role of splenic dendritic cells in CD4+ T cell priming to allogeneic RBCs. Disclosures No relevant conflicts of interest to declare.

scholarly journals Production of auto-antiidiotypic antibody during the normal immune response. VII. Analysis of the cellular basis for the increased auto-antiidiotype antibody production by aged mice.

1983 ◽  
Vol 157 (5) ◽  
pp. 1635-1645 ◽  
Author(s):  
E A Goidl ◽  
J W Choy ◽  
J J Gibbons ◽  
M E Weksler ◽  
G J Thorbecke ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Bone Marrow Cells ◽  
Aged Mice ◽  
Old Mice ◽  
Marrow Cells ◽  
Young Mice

We have previously shown that old mice produce more hapten-augmentable plaque-forming cells (PFC) than do young animals, suggesting a greater auto-antiidiotype antibody (auto anti-Id) component in their immune response. In the present studies this is confirmed serologically. The marked auto-anti-Id response of aged mice can be transferred to lethally irradiated young recipients with spleen but not bone marrow cells from old donors, suggesting that it is an intrinsic property of their peripheral B cell population and that the distribution of Id arising from the bone marrow of old and young mice is similar. In contrast with young mice the auto-anti-Id response of old animals is relatively T cell-independent and old donors do not show an increase in their ability to transfer an auto-anti-Id response after priming with TNP-F. These observations suggest that old mice behave as if already primed for auto-anti-Id production. Irradiated mice reconstituted with bone marrow cells from either young or old donors together with splenic T cells from old donors generate a relatively large auto-anti-Id response, whereas mice reconstituted with bone marrow from either young or old donors together with splenic T cells from young donors produce few hapten-augmentable PFC. It is suggested that differences in Id expression and auto-anti-Id production are the consequences of the interaction of Id (and anti-Id) arising from the marrow with anti-Id (and Id) present in the peripheral T cell population which serves as a repository of information about shifts in Id distribution, resulting from lifelong interactions with environmental and self-antigens.

scholarly journals CELL-TO-CELL INTERACTION IN THE IMMUNE RESPONSE

1971 ◽  
Vol 134 (1) ◽  
pp. 66-82 ◽  
Author(s):  
J. F. A. P. Miller ◽  
J. Sprent
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Antibody Response ◽  
B Cell ◽  
Cell Population ◽  
Thoracic Duct ◽  
Secondary Antibody ◽  
Cba Mice ◽  
Duct Cells

Collaboration between thymus-derived lymphocytes and nonthymus-derived antibody-forming cell precursors occurs in the primary antibody response of mice to heterologous erythrocytes and serum proteins. The purpose of the experiments reported here was to determine whether collaboration took place in an adoptive secondary antibody response. A chimeric population of lymphocytes was produced by reconstituting neonatally thymectomized CBA mice soon after birth with (CBA x C57BL)F1 thymus lymphocytes. These mice could be effectively primed to fowl immunoglobulin G (FγG) and their thoracic duct lymphocytes adoptively transferred memory responses to irradiated mice. The activity of these cells was impaired markedly by preincubation with CBA anti-C57BL serum and to a lesser extent by anti-θ-serum. Reversal of this deficiency was obtained by adding T cells in the form of thoracic duct cells from normal CBA mice. Cells from FγG-primed mice were at least 10 times as effective as cells from normal mice or from CBA mice primed to horse erythrocytes. These results were considered to support the concept that memory resides in the T cell population and that collaboration between T and B cells is necessary for an optimal secondary antibody response. Poor antibody responses were obtained in irradiated mice given mixtures of thoracic duct cells from primed mice and of B cells from unprimed mice (in the form of spleen or thoracic duct cells from thymectomized donors). In contrast to the situation with T cells, the deficiency in the B cell population could not be reversed by adding B cells from unprimed mice. It was considered that memory resides in B cells as well as in T cells and that priming probably entails a change in the B cell population which is fundamentally different from that produced in the T cell population.

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