The role of the thymus in development of lympho-hemopoietic tissues. The effect of thymectomy on development of blood cells, bone-marrow, spleen, and lymph nodes

1969 ◽  
Vol 164 (3) ◽  
pp. 267-281 ◽  
Author(s):  
Pitsa K. Kalpaktsoglou ◽  
E. J. Yunis ◽  
R. A. Good
Keyword(s):  
Bone Marrow ◽  
Lymph Nodes ◽  
Blood Cells ◽  
Spleen And Lymph Nodes

scholarly journals Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells

Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 5875-5884 ◽  
Author(s):  
Hideaki Tanizaki ◽  
Gyohei Egawa ◽  
Kayo Inaba ◽  
Tetsuya Honda ◽  
Saeko Nakajima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Lymph Nodes ◽  
Actin Polymerization ◽  
Cell Stimulation ◽  
T Cell Stimulation ◽  
Acquired Immune Responses

Abstract Dendritic cells (DCs) are essential for the initiation of acquired immune responses through antigen acquisition, migration, maturation, and T-cell stimulation. One of the critical mechanisms in this response is the process actin nucleation and polymerization, which is mediated by several groups of proteins, including mammalian Diaphanous-related formins (mDia). However, the role of mDia in DCs remains unknown. Herein, we examined the role of mDia1 (one of the isoforms of mDia) in DCs. Although the proliferation and maturation of bone marrow-derived DCs were comparable between control C57BL/6 and mDia1-deficient (mDia1−/−) mice, adhesion and spreading to cellular matrix were impaired in mDia1−/− bone marrow–derived DCs. In addition, fluorescein isothiocyanate-induced cutaneous DC migration to draining lymph nodes in vivo and invasive migration and directional migration to CCL21 in vitro were suppressed in mDia1−/− DCs. Moreover, sustained T-cell interaction and T-cell stimulation in lymph nodes were impaired by mDia1 deficiency. Consistent with this, the DC-dependent delayed hypersensitivity response was attenuated by mDia1-deficient DCs. These results suggest that actin polymerization, which is mediated by mDia1, is essential for several aspects of DC-initiated acquired immune responses.

scholarly journals Karyotypic polymorphism in acute myelofibrosis

Blood ◽  
1982 ◽  
Vol 60 (4) ◽  
pp. 841-844 ◽  
Author(s):  
I Shah ◽  
K Mayeda ◽  
F Koppitch ◽  
S Mahmood ◽  
B Nemitz
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Black Male ◽  
Blood Cells ◽  
Normal Karyotype ◽  
Trisomy 8 ◽  
Chronic Granulocytic Leukemia ◽  
Cytogenetic Abnormalities ◽  
Granulocytic Leukemia

Abstract Acute myelofibrosis (AMF) was diagnosed in a 59-yr-old black male in September 1978, on the basis of pancytopenia, lack of hepatosplenomegaly, fibrosis of the marrow, and paucity of teardrop red blood cells in the peripheral blood. Since then the patient has demonstrated an unusually long survival of 36 mo with a changing cytogenetic course. His initial 46, XY normal karyotype changed in 20 mo to trisomy 8, followed 1 yr later by 1:4 translocation in peripheral blood. Simultaneously with these changes, the fibrosis in the bone marrow progressively decreased, ultimately terminating in chronic granulocytic leukemia-like presentation with reversal to 46, XY karyotype. Fibroblast culture failed to show any evidence of cytogenetic abnormalities. The disappearance of fibrosis confirmed by trichrome and reticulin stains and lack of cytogenetic abnormalities in fibroblasts confirms the secondary role of fibrosis.

scholarly journals BONE MARROW AS SOURCE OF CELLS IN REACTIONS OF CELLULAR HYPERSENSITIVITY

1968 ◽  
Vol 128 (6) ◽  
pp. 1437-1449 ◽  
Author(s):  
David M. Lubaroff ◽  
Byron H. Waksman
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Skin Test ◽  
Skin Tests ◽  
Skin Reactions ◽  
Lewis Rats ◽  
Lymph Node Cells ◽  
Lymphocyte Transfer ◽  
Spleen And Lymph Nodes

The precise origin of cells infiltrating tuberculin skin reactions was studied with the technique of immunofluorescence. Thymectomized, irradiated Lewis rats were restored with bone marrow from allogeneic or F1 donors. They were passively sensitized to tuberculin by a subsequent transfer of Lewis lymph node cells and were given intradermal skin tests with tuberculoprotein. In 24 hr reactions the majority of cells were shown to be derived from the infused marrow. These results were the same regardless whether the lymphocyte transfer was performed on the day of irradiation and marrow injection or 7 days later. The cells in the tuberculin reactions, marrow, spleen, and lymph nodes not derived from the bone marrow were found to originate in the transferred lymph node cells. The relative percentages of marrow-derived and lymph node-derived cells in the tuberculin reactions remained the same during the 9–24 hr period following skin test.

Hedgehog Signaling Regulates HSC Proliferation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1390-1390
Author(s):  
Akil Merchant ◽  
Giselle Joseph ◽  
William Matsui
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Blood Cells ◽  
White Blood Cells ◽  
Wild Type ◽  
Serial Blood ◽  
Myeloid Progenitor ◽  
Hh Signaling ◽  
Progenitor Compartment

Abstract Hedgehog (Hh) signaling is essential for normal development and is dysregulated in many cancers. Hh signaling is active in normal bone marrow and the majority of acute myeloid leukemias, however, the precise role of Hh signaling and its positive effector Gli1 in normal or malignant hematopoiesis is not known. We have analyzed the bone marrow of Gli1 null mice to understand the role of this transcription factor in normal hematopoiesis in order to gain insight into its potential role in leukemia. Gli1 null mice develop normally and have normal peripheral blood counts but the bone marrow shows skewing of the c-Kit+Sca1+Lin-neg (KSL) progenitor compartment with increased CD34negKSL long-term HSC (LT-HSC) and decreased 34+KSL short-term HSC (ST-HSC). An analogous difference was observed in the c-Kit+Sca1negLinneg (KL) myeloid progenitor compartment with an increase in FcRγlowCD34+KL common myeloid progenitors (CMP) and decrease in the FcRγhighCD34+KL granulocyte monocyte progenitors (GMP). We speculated that these differences could be due to impaired cell cycle since both the ST-HSC and GMP are more proliferative than LT-HSC and CMP, respectively. Cell cycle analysis by DNA content and BrdU pulse labeling (100mg/kg IP 14 hours prior to analysis) revealed a marked decrease of proliferation in the LT-HSC, ST-HSC, CMP, and GMP compartments of Gli1 null mice. We supported this conclusion by demonstrating that the bone marrow of Gli1 null mice are relatively radio-resistant. Mice exposed to 400 cGy of total body irradiation followed with serial blood counts revealed less severe nadir, but delayed rebound of white blood cells in Gli1 null mice. We further hypothesized that although Gli1 appears to be dispensable for steady-state peripheral hematopoiesis, it might be necessary for rapid proliferation of progenitors needed during stressed hematopoiesis. In brain development, where Hh signaling is much better understood, active Hh signaling is critical for regulating proliferation of neural stem cells and Gli1 activity significantly increases after depletion of neural progenitors with chemotherapy (Bai et al., Development, 2002). To extend this observation to hematopoiesis, we treated Gli1 null mice and wild-type litter-mates with 5-fluorouracil (5-FU) at 100mg/kg and measured serial blood counts. Gli1 null mice had a delayed recovery of total white blood cells and neutrophil counts at 6 days after 5-FU, but this difference normalized by 20 days after treatment. To confirm that this difference was due to impaired proliferation and not increased sensitivity to 5-FU, we treated Gli1 null and wild-type mice with G-CSF (10mcg/kg/day) for three days to stimulate neutrophil proliferation. Confirming our hypothesis, we observed an attenuated neutrophil response in G-CSF stimulated Gli1 null mice. In summary, we have demonstrated that Gli1 loss leads to decreased HSC and myeloid progenitor proliferation, which has important functional consequences for stress hematopoiesis. These data suggest that abnormal Hh activity in leukemia may be important for driving the uncontrolled proliferation of cancer cells. Gli1 null mice were a kind gift from Alexandra Joyner, Memorial Sloan-Kettering Cancer Center

scholarly journals Deletion of Cellular Prion Protein (PrPC) Results in Peripheral Lymphocytosis and Larger Platelets

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4619-4619
Author(s):  
Yan Zheng ◽  
Guangyuan Li ◽  
Menglei Zhu ◽  
Yu Li ◽  
Howard Meyerson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Blood Cell ◽  
Lymph Nodes ◽  
Peripheral Blood ◽  
Blood Count ◽  
Complete Blood Count ◽  
Absolute Lymphocyte Count ◽  
Cellular Prion Protein ◽  
Platelet Volume ◽  
Spleen And Lymph Nodes

Abstract Cellular prion protein (PrPC) is a GPI-anchored cell surface glycoprotein that is expressed in the brain, blood, bone marrow (BM), and lymphoid tissue. PrPC can be converted post-translationally into scrapie-PrP (PrPSc), which is involved in the pathogenesis of neurodegenerative diseases including Creutzfeldt-Jakob disease, Kuru disease in humans, and scrapie and bovine spongiform encephalopathy in animals. However, the biological function of PrPSc has yet to be conclusively elucidated. In order to understand the role of PrPC in the hematopoietic system, we compared bone marrow, lymphoid organs and peripheral blood of PrPC knockout mice (KO) to age and sex-matched transgenic mice used as background controls (WT) expressing human PrPC under the control of a mouse PrPC promoter with a slightly augmented expression (2-fold) of PrPC. Complete blood count (CBC) showed a significant increase of WBC in KO mice (KO 9.03 ± 5.16 x109/L vs. WT 4.13 ± 1.87 x109/L, p = 0.0405; Table 1 and Figure 1). Further analysis of WBC differential revealed that the elevated number of WBC in KO mice was due to lymphocytosis. Specifically, KO mice had a 3-fold increase in the absolute lymphocyte count (KO 7.59 ± 4.63 x109/L vs. WT 2.90 ± 1.32 x109/L, p = 0.0303), as well as a higher lymphocyte percentage (KO 82.47 ± 4.20% vs. WT 70.19 ± 4.44%, p = 0.0011) compared to controls. KO mice also had a trend toward higher hemoglobin (KO 12.00 ± 4.40 g/dL vs. WT 9.84 ± 4.83 g/dL), RBC (KO 8.01 ± 2.87 x1012/L vs. WT 6.25 ± 3.11 x1012/L), and hematocrit (KO 43.94 ± 17.00 % vs. WT 36.04 ± 18.07 %) compared to WT mice. Additionally, platelet count in KO mice was higher than control mice (KO 762.20 ± 138.61 x 109/L vs. WT 661.80 ± 230.20 x 109/L). Of interest, the mean platelet volume (platelet size) was significantly increased in KO mice compared to controls (KO 6.00 ± 0.29 fL vs. WT 5.24 ± 0.56 fL, p =0.0140). Thus, absence of PrPC resulted in significant leukocytosis and specifically higher absolute count and percentage of lymphocytes, as well as larger platelets in peripheral blood. To further analyze if the observed lymphocytosis is due to abnormalities in hematopoiesis or lymphopoiesis, bone marrow (BM), thymus, spleen and lymph nodes from WT and KO mice were isolated and examined by flow cytometry using a comprehensive panel of fluorochrome-conjugated antibodies specific for all hematologic cell precursors/lineages. Analysis of all cell populations in each of these organs revealed no significant differences in the numbers of RBC and megakaryocyte in BM, and of lymphocytes in the thymus, spleen and lymph nodes (data no shown). Additionally, histological analysis of BM, thymus, spleen and lymph nodes tissue from KO and WT animals failed to show morphological differences between the two groups (data not shown). Therefore, lack of PrPC does not appear to affect hematopoiesis and lymphopoiesis. In summary, our findings indicate that PrPC deficiency translates into a significant increase in the number of lymphocytes in peripheral blood; however, development and maturation of lymphocytes in KO mice appeared normal. Therefore, PrPC might be critical in the survival and trafficking of lymphocytes in peripheral blood. The molecular mechanisms underlying the observed changes in lymphocytes and platelets, and whether there are any related changes in the functions of lymphocytes and platelets will be subject of future studies. Table 1. Complete blood count (CBC) of PrPC WT and KO mice WT KO p value Mean ± SD Mean ± SD WBC (109/L) 4.13 ± 1.87 9.03 ± 5.16 0.0405 Absolute lymphocyte count (109/L) 2.90 ± 1.32 7.59 ± 4.63 0.0303 Lymphocyte (%) 70.19 ± 4.44 82.47 ± 4.20 0.0011 RBC (1012/L) 6.25 ± 3.11 8.01 ± 2.87 0.1898 HB (g/dL) 9.84 ± 4.83 12.00 ± 4.40 0.2404 HCT (%) 36.04 ± 18.07 43.94 ± 17.00 0.2618 PLT (109/L) 661.80 ± 230.20 762.20 ± 138.61 0.2138 MPV (fL) 5.24 ± 0.56 6.00 ± 0.29 0.0140 SD: Standard deviation; WBC: White blood cell; RBC: Red blood cell; HB: Hemoglobin; HCT: Hematocrit; RDW: Red cell distribution width; PLT: Platelet; MPV: Mean platelet volume Figure 1. PrPC deficiency results in lymphocytosis in peripheral blood. Figure 1. PrPC deficiency results in lymphocytosis in peripheral blood. Disclosures No relevant conflicts of interest to declare.

scholarly journals Karyotypic polymorphism in acute myelofibrosis

Blood ◽  
1982 ◽  
Vol 60 (4) ◽  
pp. 841-844
Author(s):  
I Shah ◽  
K Mayeda ◽  
F Koppitch ◽  
S Mahmood ◽  
B Nemitz
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Black Male ◽  
Blood Cells ◽  
Normal Karyotype ◽  
Trisomy 8 ◽  
Chronic Granulocytic Leukemia ◽  
Cytogenetic Abnormalities ◽  
Granulocytic Leukemia

Acute myelofibrosis (AMF) was diagnosed in a 59-yr-old black male in September 1978, on the basis of pancytopenia, lack of hepatosplenomegaly, fibrosis of the marrow, and paucity of teardrop red blood cells in the peripheral blood. Since then the patient has demonstrated an unusually long survival of 36 mo with a changing cytogenetic course. His initial 46, XY normal karyotype changed in 20 mo to trisomy 8, followed 1 yr later by 1:4 translocation in peripheral blood. Simultaneously with these changes, the fibrosis in the bone marrow progressively decreased, ultimately terminating in chronic granulocytic leukemia-like presentation with reversal to 46, XY karyotype. Fibroblast culture failed to show any evidence of cytogenetic abnormalities. The disappearance of fibrosis confirmed by trichrome and reticulin stains and lack of cytogenetic abnormalities in fibroblasts confirms the secondary role of fibrosis.

scholarly journals Megakaryopoiesis and Platelet Biology: Roles of Transcription Factors and Emerging Clinical Implications

2021 ◽  
Vol 22 (17) ◽  
pp. 9615
Author(s):  
Ji-Yoon Noh
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Transcription Factors ◽  
Blood Cells ◽  
Thrombus Formation ◽  
Critical Role ◽  
Clinical Implications ◽  
Disease Development ◽  
Hematopoietic Stem

Platelets play a critical role in hemostasis and thrombus formation. Platelets are small, anucleate, and short-lived blood cells that are produced by the large, polyploid, and hematopoietic stem cell (HSC)-derived megakaryocytes in bone marrow. Approximately 3000 platelets are released from one megakaryocyte, and thus, it is important to understand the physiologically relevant mechanism of development of mature megakaryocytes. Many genes, including several key transcription factors, have been shown to be crucial for platelet biogenesis. Mutations in these genes can perturb megakaryopoiesis or thrombopoiesis, resulting in thrombocytopenia. Metabolic changes owing to inflammation, ageing, or diseases such as cancer, in which platelets play crucial roles in disease development, can also affect platelet biogenesis. In this review, I describe the characteristics of platelets and megakaryocytes in terms of their differentiation processes. The role of several critical transcription factors have been discussed to better understand the changes in platelet biogenesis that occur during disease or ageing.

Homeostatic Role of the Krüppel-Like Factor 4 (KLF4) in Proliferation and Differentiation of Primitive Hematopoietic Progenitor Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1497-1497 ◽  
Author(s):  
Chun Shik Park ◽  
Takeshi Yamada ◽  
H. Daniel Lacorazza
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Proliferative Potential ◽  
Dependent Manner ◽  
Hematopoietic Stem ◽  
Deficient Mice

Abstract Abstract 1497 Poster Board I-520 KLF4 is a tumor suppressor in the gastrointestinal tract known to induce cell cycle arrest in a cell context dependent manner. We recently reported that KLF4 maintains quiescence of T lymphocytes downstream of T-cell receptor signaling (Yamada et al., Nature Immunology, 2009). The role of KLF4 in reprogramming adult somatic cells into pluripotent stem cells along with Oct3/4, c-Myc and Sox2 suggests that KLF4 restricts proliferation of undifferentiated cells. In spite of a redundant role of KLF4 in fetal liver hematopoietic stem cells (HSC), its role in the maintenance of adult bone marrow HSCs has not been studied yet. To study the role of KLF4 in the hematopoietic system we used gain- and loss-of-function mouse models. Retroviral transfer of KLF4 into wild type bone marrow (BM) cells led to significant reduction of colony forming units (CFU) in methylcellulose cultures due to increased apoptosis and lower proliferation. Then, Mx1-Cre was used to induce deletion of Klf4-floxed mice by polyI:C administration. Analysis of peripheral blood cells up to 6-9 months post polyI:C administration showed significant reduction of monocytes, as previously reported, and expansion of CD8+CD44+ T cells due to their increased proliferative potential. BM cells from Klf4-deficient mice exhibited increased number of myeloid progenitor cells measured by flow cytometry (Lin-Sca-1-c-kit+FcRII/III+CD34+ cells), CFU and CFU-S8. Cytoablation with 5-fluorouracil (5-FU) showed lower nadir of peripheral white blood cells in Klf4-deficient mice compared to control mice. In spite of normal multilineage reconstitution in BM transplants experiments, competitive reconstitution with Klf4-deficient and normal BM cells resulted in reduced contribution of Klf4-deficient cells to peripheral blood, likely due to homing and proliferative differences. Collectively, our data shows that KLF4 has an important role in function of hematopoietic stem and progenitor cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals THE ROLE OF LYMPHOCYTES IN THE SENSITIZATION OF RATS TO RENAL HOMOGRAFTS

1965 ◽  
Vol 122 (2) ◽  
pp. 347-360 ◽  
Author(s):  
S. Strober ◽  
J. L. Gowans
Keyword(s):  
Lymph Nodes ◽  
Thoracic Duct ◽  
Femoral Vein ◽  
F1 Hybrid ◽  
Duct Cells ◽  
Degree Of Sensitization ◽  
Spleen And Lymph Nodes

In order to study the role of blood-borne small lymphocytes in the sensitization of rats to renal homografts 2 techniques for the perfusion of isolated rat kidneys were employed: (a) the in vitro perfusion of kidneys with thoracic duct cells suspended in either an artificial medium or in blood; the perfusates were then injected into rats syngeneic with the lymphocyte donors; (b) the in vivo perfusion of kidneys with blood issuing from the femoral artery and returning to the femoral vein of living rats. The degree of sensitization conferred on the recipients by the perfusates was assessed by applying a skin homograft from the kidney donor and scoring the epithelial necrosis at 6 days. The in vitro experiments indicated that parental strain thoracic duct cells, which had passed through an F1 hybrid kidney could confer upon a parental rat sensitivity to an F1 skin graft. Several perfusions with radioactively labelled lymphocytes showed that the injected cells migrated to the lymph nodes and spleen of the recipients Labelled large pyroninophilic cells were occasionally seen in the spleen and lymph nodes of recipients, and it was suggested that these had arisen from the injected cells. Although the in vitro perfusions with blood indicated that renal homografts might sensitize their hosts within 1 hour, the in vivo perfusions suggested that about 5 to 12 hours were required. The more rapid sensitization in vitro was possibly due to the more frequent opportunity for contact between lymphocytes and kidney vascular endothelium which was afforded by the conditions in vitro.

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