scholarly journals Peripheral lymph node helper T-cell recovery after syngeneic bone marrow transplantation in mice prepared with either gamma-irradiation or busulfan

Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1436-1445 ◽  
Author(s):  
WE Samlowski ◽  
BA Araneo ◽  
MO Butler ◽  
MC Fung ◽  
HM Johnson
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Lymph Nodes ◽  
Gamma Irradiation ◽  
Peripheral Lymph Node ◽  
Helper T Cell ◽  
Peripheral Lymph ◽  
Preparative Regimen

Abstract The optimum marrow ablative regimen for preparing recipients of bone marrow transplantation (BMT) has not been established. gamma- Irradiation, but not busulfan, produces a characteristic microvascular injury pattern which results in depressed capacity of normal lymphocytes to localize into the lymph nodes of syngeneic murine BMT recipients. Since peripheral lymph nodes are important sites for initiation and amplification of immune responses, the preparative regimen might delay recovery of regionally compartmentalized immune functions after BMT. We evaluated the effects of busulfan and gamma- irradiation on the phenotypic and functional reconstitution of helper T- cell function within the peripheral lymph nodes of BMT recipients. Both marrow ablative regimens caused a protracted delay in regeneration of peripheral lymph node CD4+ T cells. Specific helper T-cell functions, such as contact hypersensitivity and alloantigen responses, remained significantly depressed in the lymph nodes of irradiated mice for prolonged periods (up to 60 weeks). These responses recovered more rapidly in busulfan-treated BMT recipients. In contrast, the capacity of peripheral lymph node T cells to provide “help” for antigen-specific immunoglobulin production was only transiently depressed by either preparative regimen. Our experiments confirm the hypothesis that the marrow ablative regimen, particularly gamma-irradiation, may contribute to the period of immunodeficiency which follows BMT. The pattern of immune recovery observed suggests that preparative total body irradiation (TBI) may selectively depress the regional recovery of the TH1 [interleukin-2 (IL-2) and gamma-interferon (gamma-IFN) secreting] lymphocyte subset.

scholarly journals Peripheral lymph node helper T-cell recovery after syngeneic bone marrow transplantation in mice prepared with either gamma-irradiation or busulfan

Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1436-1445 ◽  
Author(s):  
WE Samlowski ◽  
BA Araneo ◽  
MO Butler ◽  
MC Fung ◽  
HM Johnson
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Lymph Nodes ◽  
Gamma Irradiation ◽  
Peripheral Lymph Node ◽  
Helper T Cell ◽  
Peripheral Lymph ◽  
Preparative Regimen

The optimum marrow ablative regimen for preparing recipients of bone marrow transplantation (BMT) has not been established. gamma- Irradiation, but not busulfan, produces a characteristic microvascular injury pattern which results in depressed capacity of normal lymphocytes to localize into the lymph nodes of syngeneic murine BMT recipients. Since peripheral lymph nodes are important sites for initiation and amplification of immune responses, the preparative regimen might delay recovery of regionally compartmentalized immune functions after BMT. We evaluated the effects of busulfan and gamma- irradiation on the phenotypic and functional reconstitution of helper T- cell function within the peripheral lymph nodes of BMT recipients. Both marrow ablative regimens caused a protracted delay in regeneration of peripheral lymph node CD4+ T cells. Specific helper T-cell functions, such as contact hypersensitivity and alloantigen responses, remained significantly depressed in the lymph nodes of irradiated mice for prolonged periods (up to 60 weeks). These responses recovered more rapidly in busulfan-treated BMT recipients. In contrast, the capacity of peripheral lymph node T cells to provide “help” for antigen-specific immunoglobulin production was only transiently depressed by either preparative regimen. Our experiments confirm the hypothesis that the marrow ablative regimen, particularly gamma-irradiation, may contribute to the period of immunodeficiency which follows BMT. The pattern of immune recovery observed suggests that preparative total body irradiation (TBI) may selectively depress the regional recovery of the TH1 [interleukin-2 (IL-2) and gamma-interferon (gamma-IFN) secreting] lymphocyte subset.

Immunopathology of ATG Prior to Bone Marrow Transplantation in Mouse Model

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4603-4603
Author(s):  
Behnam Sadeghi ◽  
Sulaiman Al Hashmi ◽  
Zuzana Hassan ◽  
Bjorn Rozell ◽  
Manuchehr Abedi-Valugerdi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Mouse Model ◽  
Lymph Nodes ◽  
Cell Population ◽  
Marrow Transplantation ◽  
Cell Phenotype ◽  
Administration Time

Abstract Introduction: Polyclonal anti-thymocyte globulin (ATG) is mainly used in hematopoietic stem cell transplantation, as a prevention for graft rejection as well as for GVHD. Immunosuppressive properties of ATG have been considered primarily from the depletion of peripheral lymphocytes. However direct or indirect effects of ATG on other immune components still is controversial. In the present study we evaluated the immunopathologic effects of ATG on immune system in a mouse model. Methods Ten to fourteen weeks old BALB/c and C57BL/6 mice, were injected intra- peritoneally or intravenously with different doses of ATG (0.2mg/kg -25mg/kg) at three dosage schedules. Considering bone marrow transplantation as day 0, ATG were given at days -10, -7 and -5 or -7, -5 and -1 or -5, -3 and -1. At day 0, mice were killed; spleen (SP), bone marrow (BM), lymph nodes (LN) and thymus were removed and analyzed for T-, B-, DC, NK-, T-reg and myeloid cells. To evaluate the efficacy of immunosuppressive effect of ATG, a group of BALB/c mice were conditioned using busulfan (Bu) and ATG and compared to a control group of BALB/c conditioned with Bu (80mg/kg) followed by cyclophosphamide (200mg/kg). Both groups transplanted with BM and spleen cells from C57BL/6 and followed for engraftment and/or GVHD. Results The administration of ATG (0.2- 4.5mg/kg) has resulted in an increase in spleen cellularity while in lymph node and thymus a decreased cellularity was observed. We have found that injecting 4.5mg/kg of ATG at day -7, -5 and -3 significantly decreased T-cell population in spleen and LN compare to Bu-Cy conditioning. The ratio CD4/CD8 increased after ATG treatment showing that CD8 cells are six-fold more sensitive to ATG treatment compared to CD4 lymphocyte. Interestingly T-reg cell population increase after ATG at day 0, however, the increment was negatively correlated with the administration time and positively correlated with the dose. ATG treatment has resulted in an increase in B-cell population by two- and three- fold in spleen and lymph nodes, respectively. Moreover, 1.2- to 3.5-fold increase in DCs, NK and myeloid cells was observed in SP and LN. Thymus cellularity and cell phenotype was less affected while BM cellularity was not affected by ATG treatment. No differences in the ATG effect on cellularity or cell phenotype between IP and IV route was observed. Despite the high immunosuppressive effect observed in T-cell population compared to that seen in Bu-Cy conditioning, no chimerism was observed when Cy was substituted with ATG (4.5 – 10 mg/kg). Conclusion No donor chimerism could be obtained using ATG as a single agent up to 25mg/kg. ATG dose and the administration time are important factors affecting the repopulation of residual T-cells in spleen and lymph node that have to be considered in bone marrow transplantation setting.

scholarly journals Notch-dependent T-lineage commitment occurs at extrathymic sites following bone marrow transplantation

Blood ◽  
2006 ◽  
Vol 107 (9) ◽  
pp. 3511-3519 ◽  
Author(s):  
Ivan Maillard ◽  
Benjamin A. Schwarz ◽  
Arivazhagan Sambandam ◽  
Terry Fang ◽  
Olga Shestova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Marrow Transplantation ◽  
T Cell Development ◽  
Lineage Commitment ◽  
Adult Mice ◽  
Multipotent Progenitors ◽  
Peripheral Lymph ◽  
Differentiation Pathways

Early T-lineage progenitors (ETPs) arise after colonization of the thymus by multipotent bone marrow progenitors. ETPs likely serve as physiologic progenitors of T-cell development in adult mice, although alternative T-cell differentiation pathways may exist. While we were investigating mechanisms of T-cell reconstitution after bone marrow transplantation (BMT), we found that efficient donor-derived thymopoiesis occurred before the pool of ETPs had been replenished. Simultaneously, T lineage–restricted progenitors were generated at extrathymic sites, both in the spleen and in peripheral lymph nodes, but not in the bone marrow or liver. The generation of these T lineage–committed cells occurred through a Notch-dependent differentiation process. Multipotent bone marrow progenitors efficiently gave rise to extrathymic T lineage–committed cells, whereas common lymphoid progenitors did not. Our data show plasticity of T-lineage commitment sites in the post-BMT environment and indicate that Notch-driven extrathymic Tlineage commitment from multipotent progenitors may contribute to early T-lineage reconstitution after BMT.

NK Cells Induce Alloreactive Donor T Cell Apoptosis and Decrease Proliferation in GVHD Induction.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2162-2162
Author(s):  
Janelle A. Olson ◽  
Dennis B. Leveson-Gower ◽  
Andreas Beilhack ◽  
Robert S. Negrin
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Nk Cells ◽  
Nk Cell ◽  
Cell Trafficking ◽  
Peripheral Lymph ◽  
Donor T Cells

Abstract Natural Killer (NK) cells have the ability to suppress graft-versus-host disease (GVHD) while inducing a graft-versus-tumor response (GVT) during allogeneic bone marrow transplantation (BMT). Previous studies in allogeneic BMT models have shown NK cell trafficking to and proliferation in lymphoid organs and GVHD target organs, which are also sites of donor T cell trafficking. This study aims to investigate the impact of NK cells on alloreactive, GVHD-inducing donor T cells. Interleukin-2 activated allogeneic NK cells isolated from C57Bl6 (H–2b) or FVB (H–2q) animals were transplanted along with T cell-depleted bone marrow into lethally irradiated BALB/c (H–2d) mice, followed 2 days later by luciferase-expressing CD4+ and CD8+ conventional T cells from the same donor strain (NK+Tcon group). Control mice received lethal irradiation and T cell-depleted bone marrow on day 0, and luciferase-expressing T cells on day 2 after transplant (Tcon group). Bioluminescence imaging of NK+Tcon mice revealed a significantly lower T cell bioluminescent signal (p=0.03 for FVB into BALB/c on day 6) than from Tcon mice. CFSE proliferation analysis of alloreactive T cells on day 3 after transplant showed no significant change in the percent of donor T cells that have divided in the spleen, and only a slight decrease in the percent of T cells that have divided in the lymph nodes when NK cells are present. However, at this timepoint 82% of the proliferating cells have divided past the third generation, in contrast to 64% in the NK+Tcon mice. Donor T cells in both groups become equally activated in vivo, expressing similar levels of the early-activation marker CD69. T cells re-isolated from NK+Tcon animals at day 5 stained 2 to 10-fold higher for the TUNEL apoptosis marker than those from Tcon mice in the mesenteric and peripheral lymph nodes, respectively (p<0.0001). Additionally, decreased numbers of T cells were re-isolated from the peripheral lymph nodes in the NK+Tcon group as compared to the Tcon group. This increase in TUNEL staining was not seen when the transplanted NK cells were isolated from a perforin-deficient donor. This indicates that NK cells in lymph nodes use a perforin-dependent mechanism to increase apoptosis in proliferating, alloreactive donor T-cells, which are syngeneic to the transplanted NK cells. Donor T cells re-isolated from the lymph nodes of transplanted mice up-regulate the NKG2D ligand Rae1γ as compared to naïve T cells, as shown by FACS. This suggests that NK cells may cause direct lysis of alloreactive donor T cells in vivo during GVHD induction, mediated by the NK cell activating receptor NKG2D. This study provides crucial mechanistic information regarding the function of NK cells in suppressing GVHD.

Host-specific donor helper T-cell precursors as predictors of acute GVHD and relapse in HLA-identical siblings bone marrow transplantation (BMT)

1996 ◽  
Vol 47 (1-2) ◽  
pp. 109
Author(s):  
S. Lachance ◽  
S. LeGouvello ◽  
M. Kuentz ◽  
C. Cordonnier ◽  
F. Bernaudin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Helper T Cell

scholarly journals Immunohistologic and functional characterization of a vascular addressin involved in lymphocyte homing into peripheral lymph nodes.

1988 ◽  
Vol 107 (5) ◽  
pp. 1853-1862 ◽  
Author(s):  
P R Streeter ◽  
B T Rouse ◽  
E C Butcher
Keyword(s):  
Endothelial Cells ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Peyer's Patches ◽  
Peripheral Lymph Node ◽  
Lymphocyte Homing ◽  
Tissue Specific ◽  
Peripheral Lymph

The tissue localization or "homing" of circulating lymphocytes is directed in part by specialized vessels that define sites of lymphocyte exit from the blood. In peripheral lymph nodes, mucosal lymphoid tissues (Peyer's patches and appendix), and sites of chronic inflammation, for example, lymphocytes leave the blood by adhering to and migrating between those endothelial cells lining postcapillary high endothelial venules (HEV). Functional analyses of lymphocyte interactions with HEV have shown the lymphocytes can discriminate between HEV in different tissues, indicating that HEV express tissue-specific determinants or address signals for lymphocyte recognition. We recently described such a tissue-specific "vascular addressin" that is selectively expressed by endothelial cells supporting lymphocyte extravasation into mucosal tissues and that appears to be required for mucosa-specific lymphocyte homing (Streeter, P. R., E. L. Berg, B. N. Rouse, R. F. Bargatze, and E. C. Butcher. 1988. Nature (Lond.). 331:41-46). Here we document the existence and tissue-specific distribution of a distinct HEV differentiation antigen. Defined by monoclonal antibody MECA-79, this antigen is expressed at high levels on the lumenal surface and in the cytoplasm of HEV in peripheral lymph nodes. By contrast, although MECA-79 stains many HEV in the mucosal Peyer's patches, expression in most cases is restricted to the perivascular or ablumenal aspect of these venules. In the small intestine lamina propria, a mucosa-associated site that supports the extravasation of lymphocytes, venules do not stain with MECA-79. Finally, we demonstrate that MECA-79 blocks binding of both normal lymphocytes and a peripheral lymph node-specific lymphoma to peripheral lymph node HEV in vitro and that it also inhibits normal lymphocyte homing to peripheral lymph nodes in vivo without significantly influencing lymphocyte interactions with Peyer's patch HEV in vitro or in vivo. Thus, MECA-79 defines a novel vascular addressin involved in directing lymphocyte homing to peripheral lymph nodes.

Orchidectomy and the immune response I. Effect of orchidectomy on lymphoid tissues of mice

1974 ◽  
Vol 185 (1081) ◽  
pp. 425-436 ◽  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Lymphoid Tissues ◽  
Spleen Size ◽  
Thymic Involution ◽  
Peripheral Lymph Node ◽  
Peripheral Lymph ◽  
Lymph Node Enlargement ◽  
Spleen Mass ◽  
Lymph Node Mass

The effects of pre- and postpuberal orchidectomy on the lymphoid tissues of mice have been studied. Prepuberal orchidectomy delayed the normal rate of thymic involution and caused relative hypertrophy of the thymus which was maximal 1 month after surgery. There was also enlargement of the peripheral lymph nodes to reach a sustained maximum by 6 weeks and also an increase of spleen size. Histological examination of the enlarged thymus showed widening of the cortex and medulla with increased cell density. The enlarged peripheral lymph nodes showed widening of the paracortical area which is thymus dependent. Synchronous thymectomy and orchidectomy prevented the lymph node enlargement that follows orchidectomy alone, but it did not affect the increase of spleen size until 3 months after surgery. After postpuberal orchidectomy thymic size increased to a maximum at 1 month and the increase of peripheral lymph node mass and spleen mass was less than the changes following prepuberal surgery ; only 3 months after operation was the lymph node mass of orchidectomized mice significantly greater than controls and changes in spleen mass were only apparent after correction for changes in body mass.

scholarly journals Rapid CD4+ T-Cell Loss Induced by Human Immunodeficiency Virus Type 1NC in Uninfected and Previously Infected Chimpanzees

2001 ◽  
Vol 75 (3) ◽  
pp. 1533-1539 ◽  
Author(s):  
Francis J. Novembre ◽  
Juliette de Rosayro ◽  
Soumya Nidtha ◽  
Shawn P. O'Neil ◽  
Terri R. Gibson ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Lymph Node ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cell Loss ◽  
Peripheral Lymph Node ◽  
Peripheral Lymph ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT To investigate the pathogenicity of a virus originating in a chimpanzee with AIDS (C499), two chimpanzees were inoculated with a plasma-derived isolate termed human immunodeficiency virus type 1NC (HIV-1NC). A previously uninfected chimpanzee, C534, experienced rapid peripheral CD4+ T-cell loss to fewer than 26 cells/μl by 14 weeks after infection. CD4+ T-cell depletion was associated with high plasma HIV-1 loads but a low virus burden in the peripheral lymph node. The second chimpanzee, C459, infected 13 years previously with HIV-1LAV, experienced a more protracted course of peripheral CD4+ T-cell loss after HIV-1NCinoculation, resulting in fewer than 200 cells/μl by 96 weeks postinoculation. The quantities of viral RNA in the plasma and peripheral lymph node from C459 were below the lower limits of detection prior to inoculation with HIV-1NC but were significantly and persistently increased after superinfection, with HIV-1NC representing the predominant viral genotype. These results show that viruses derived from C499 are more pathogenic for chimpanzees than any other HIV-1 isolates described to date.

Sign in / Sign up

Export Citation Format

Share Document