scholarly journals SYNERGISM OF THYMUS AND BONE MARROW IN THE PRODUCTION OF GRAFT-VERSUS-HOST SPLENOMEGALY IN X-IRRADIATED HOSTS

1970 ◽  
Vol 132 (2) ◽  
pp. 317-328 ◽  
Author(s):  
Henry R. Hilgard
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Parental Strain ◽  
Bone Marrow Cells ◽  
Immunologic Response ◽  
F1 Hybrid ◽  
Graft Versus Host ◽  
Humoral Immune ◽  
Thymus Cells ◽  
Marrow Cells

Graft-versus-host splenomegaly may be elicited from 500 R X-irradiated F1 hybrid hosts if the hosts are injected with bone marrow cells and thymus cells from parental strain donors. Cells from thymus only or bone marrow only will not elicit graft-versus-host splenomegaly in these hosts. In this requirement for cells from both sources, the bone marrow cells play a nonimmunologic, proliferative role in the splenomegaly, and the thymus cells carry out the immunologic attack. Thus the mechanism of this synergism is quite different from that reported for the humoral immune response to sheep erythrocytes in which both thymus and marrow interact in the production of the specific immunologic response itself.

scholarly journals DISTINCT EVENTS IN THE IMMUNE RESPONSE ELICITED BY TRANSFERRED MARROW AND THYMUS CELLS

1969 ◽  
Vol 130 (6) ◽  
pp. 1243-1261 ◽  
Author(s):  
G. M. Shearer ◽  
G. Cudkowicz
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Bone Marrow Cells ◽  
Second Step ◽  
Cell Divisions ◽  
Cellular Events ◽  
Antigen Complex ◽  
Fresh Bone ◽  
Thymus Cells ◽  
Marrow Cells

Marrow cells and thymocytes of unprimed donor mice were transplanted separately into X-irradiated syngeneic hosts, with or without sheep erythrocytes (SRBC). Antigen-dependent changes in number or function of potentially immunocompetent cells were assessed by retransplantation of thymus-derived cells with fresh bone marrow cells and SRBC; of marrow-derived cells with fresh thymocytes and SRBC; and of thymus-derived with marrow-derived cells and SRBC. Plaque-forming cells (PFC) of the direct (IgM) and indirect (IgG) classes were enumerated in spleens of secondary host mice at the time of peak responses. By using this two-step design, it was shown (a) that thymus, but not bone marrow, contained antigen-reactive cells (ARC) capable of initiating the immune response to SRBC (first step), and (b) that the same antigen complex that activated thymic ARC was required for the subsequent interaction between thymus-derived and marrow cells and/or for PFC production (second step). Thymic ARC separated from marrow cells but exposed to SRBC proliferated and generated specific inducer cells. These were the cells that interacted with marrow precursors of PFC to form the elementary units for plaque responses to SRBC, i.e. the class- and specificity-restricted antigen-sensitive units. It was estimated that each ARC generated 80–800 inducer cells in 4 days by way of a minimum of 6–10 cell divisions. On the basis of the available evidence, a simple model was outlined for cellular events in the immune response to SRBC.

scholarly journals Association of immunity and tolerance to host H-2 determinants in irradiated F1 hybrid mice reconstituted with bone marrow cells from one parental strain.

1975 ◽  
Vol 142 (2) ◽  
pp. 321-331 ◽  
Author(s):  
J Sprent ◽  
H V Boehmer ◽  
M Nabholz
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Thoracic Duct ◽  
Parental Strain ◽  
Bone Marrow Cells ◽  
Third Party ◽  
F1 Hybrid ◽  
Host Type ◽  
Hybrid Mice ◽  
Marrow Cells

Semiallogenetic radiation chimeras were prepared by injecting heavily irradiated F1 hybrid mice with bone marrow cells from one parental strain; the bone marrow cells were treated with anti-theta serum and complement to remove T cells and injected in large numbers (2 times 10-7 cells). The mice survived in excellent health until sacrifice 6 mo later. Thoracic duct cannulation at this stage showed that the mice possessed normal numbers of recirculating lymphocytes. Close to 100% of thoracic duct lymphocytes and lymph node cells were shown to be of donor strain origin. The capacity of lymphocytes from the chimeras to respond to host-type determinants was tested in mixed leukocyte culture and in an assay for cell-mediated lympholysis (CML). Mixed leukocyte reactions (MLR) were measured both in vitro and in vivo; tumor cells and phytohemmaglutinin-stimulated blast cells were used as target cells for measuring CML. While responding normally to third party determinants, cells from the chimeras gave a definite, though reduced MLR when exposed to host-type determinants. However, this proliferative response to host-type determinants, unlike that to third party determinants, was not associated with differentiation into cytotoxic lymphocytes. No evidence could be found that unresponsiveness in this situation was due to blocking serum factors or suppressor T cells. It is argued that the results support the concept that lymphocytes responsive in mixed leukocyte culture have a different specificity to those exerting cell-mediated lympholysis.

Donor-derived IL-15 is critical for acute allogeneic graft-versus-host disease

Blood ◽  
2005 ◽  
Vol 105 (2) ◽  
pp. 894-901 ◽  
Author(s):  
Bradley W. Blaser ◽  
Sameek Roychowdhury ◽  
Daniel J. Kim ◽  
Noah R. Schwind ◽  
Darshna Bhatt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Cell Function ◽  
Bone Marrow Cells ◽  
Effector Memory ◽  
F1 Hybrid ◽  
Host Disease ◽  
Graft Versus Host ◽  
Marrow Cells

AbstractInterleukin-15 (IL-15) is a pleiotropic proinflammatory cytokine with inefficient posttranscriptional processing. We hypothesized that endogenous IL-15 could affect disease progression in the well-described C57Bl/6 (B6) → (C57Bl/6 × DBA/2) F1 hybrid (B6D2F1) murine model of acute allogeneic graft-versus-host disease (GVHD). B6D2F1 allogeneic recipients received transplants of IL-15-/- B6 bone marrow cells or B6 bone marrow cells expressing a murine IL-15 transgene (IL-15 tg) modified for efficient translation and secretion. Mice that received transplants of IL-15-/- B6 bone marrow cells displayed a significantly longer median survival time (MST) compared with mice that received transplants of wild-type (wt) B6 bone marrow; in contrast, mice that received transplants of IL-15 tg B6 bone marrow cells had a dramatically decreased MST. This decrease in survival was associated with a substantial activation and expansion of effector-memory (CD44highCD62Llow) CD8+ T lymphocytes. Finally, in vivo depletion of either CD4+ or CD8+ T lymphocyte subsets significantly prolonged survival in mice receiving IL-15 tg B6 marrow, while depletion of both CD4+ and CD8+ T cells provided complete protection from acute GVHD. We thus show that acute GVHD is attenuated in the absence of donor bone marrow–derived IL-15 and conclude that donor-derived IL-15 is a critical mediator of T-cell function in acute GVHD.

Synergism between Thymocytes and Bone Marrow Cells in a Graft versus Host Reaction

Nature ◽  
1970 ◽  
Vol 227 (5253) ◽  
pp. 71-72 ◽  
Author(s):  
JOHN BARCHILON ◽  
RICHARD K. GERSHON
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Graft Versus Host Reaction ◽  
Host Reaction ◽  
Graft Versus Host ◽  
Marrow Cells

scholarly journals THE ROLE OF THYMUS AND BONE MARROW CELLS IN DELAYED HYPERSENSITIVITY

1971 ◽  
Vol 134 (5) ◽  
pp. 1144-1154 ◽  
Author(s):  
David G. Tubergen ◽  
Joseph D. Feldman
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Specific Antigen ◽  
Delayed Hypersensitivity ◽  
Cell Type ◽  
Skin Reactions ◽  
Lymph Node Cells ◽  
Thymus Cells ◽  
Marrow Cells

Adoptive transfer experiments were performed to define the immunological role of thymus and bone marrow cells in the induction of delayed hypersensitivity (DH). The results indicated the following, (a) Bone marrow from immune donors contained cells capable of being stimulated by antigen to initiate the expression of DH. (b) Bone marrow from nonimmune or tolerant donors contained cells that were needed to complete the expression of DH after the infusion of immune lymph node cells. (c) Normal bone marrow and thymus cells cooperated in the irradiated recipient to induce the most vigorous skin reactions to specific antigen; these reactions were seen only when the recipients were stimulated by antigen. Either cell type alone was ineffective. (d) In the presence of tolerant bone marrow cells, thymus cells from immune donors gave a more vigorous response than did thymus cells from normal or tolerant donors. (e) There was suggestive evidence that thymus cells were the source of trigger elements that initiated DH. (f) Antigen in the irradiated recipient was necessary to induce DH after infusion of bone marrow cells alone, or bone marrow and thymus cells together.

scholarly journals CONTRIBUTION OF A THYMIC HUMORAL FACTOR TO THE DEVELOPMENT OF AN IMMUNOLOGICALLY COMPETENT POPULATION FROM CELLS OF MOUSE BONE MARROW

1971 ◽  
Vol 134 (3) ◽  
pp. 786-800 ◽  
Author(s):  
Myra Small ◽  
Nathan Trainin
Keyword(s):  
Bone Marrow ◽  
Lymphoid Tissue ◽  
Host Response ◽  
Bone Marrow Cells ◽  
Immune Reactivity ◽  
Mouse Bone Marrow ◽  
Graft Versus Host ◽  
Peripheral Lymphoid Tissue ◽  
Marrow Cells

The hypothesis that cells located in mouse bone marrow can acquire immunological competence by a process that involves interaction with a noncellular component of the thymus was tested using an in vitro assay of graft-versus-host reactivity as a criterion of cell competence. When suspensions of C57BL bone marrow cells were incubated in thymus extract and injected into mice incapable of inducing a response in the graft-versus-host assay as a result of neonatal thymectomy, or adult thymectomy plus irradiation, or because of genetic similarity with the (C3H x C57BL)F1 tissue used for challenge in the assay, competent cells were recovered from the spleens of the injected mice. The reactive cells were shown to be of bone marrow origin since immune reactivity was related to the genetic makeup of the bone marrow cells rather than that of the intermediate recipients. A thymic factor was involved in the process leading to immune reactivity by these cells, as bone marrow cells incubated in xenogeneic or syngeneic thymic extracts induced a graft-versus-host response after passage through nonresponsive mice, whereas incubation of bone marrow cells in xenogeneic lymph node or spleen extracts or in culture medium only did not lead to subsequent reactivity. Participation of peripheral lymphoid tissue seemed essential in this process since bone marrow cells tested directly after exposure to thymic extract failed to induce a graft-versus-host response. C57BL bone marrow cells exposed to thymus extract and cultured together with fragments of (C3H x C57BL)F1 spleen tissue in vitro were competent to induce a graft-versus-host response; thus, these components would seem to be sufficient as well as necessary for the immunodifferentiation process leading to graft-versus-host activity. It is concluded that one step in the process by which bone marrow cells acquire competence vis-a-vis the graft-versus-host response depends upon a thymic agent that is noncellular and extractable, and that another stage in this process is under the influence of components found within the peripheral lymphoid tissue environment. It is suggested that differentiation of precursor cells to competence could occur by progressive development of the cells in separate compartments of the lymphoid system.

Graft-versus-host reaction-like phenomenon Induced by BCG in mice lethally irradiated and transferred with syngeneic bone marrow cells

1977 ◽  
Vol 29 (2) ◽  
pp. 312-321 ◽  
Author(s):  
Shizuko Muraoka ◽  
Kikuo Nomoto ◽  
Tsunenori Miyake ◽  
Yoshiro Imada ◽  
Kenji Takeya
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Graft Versus Host Reaction ◽  
Host Reaction ◽  
Graft Versus Host ◽  
Marrow Cells

scholarly journals STUDIES ON CHARACTERIZATION OF THE LYMPHOID TARGET CELL FOR ACTIVITY OF A THYMUS HUMORAL FACTOR

1973 ◽  
Vol 138 (1) ◽  
pp. 130-142 ◽  
Author(s):  
Varda Rotter ◽  
Amiela Globerson ◽  
Ichiro Nakamura ◽  
Nathan Trainin
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Cell Activity ◽  
Humoral Factor ◽  
Target Cells ◽  
Total Body ◽  
Thymus Cells ◽  
Marrow Cells

The immune response to SRBC was measured in the spleens of adult thymectomized, total body irradiated mice injected with various combinations of thymus and bone marrow cells together with thymic humoral factor (THF). It was found that the number of plaque-forming cells was significantly increased when THF was given in vivo immediately after thymus cell administration or when thymus cells were incubated in THF before injection. On the other hand, bone marrow cells equally treated did not manifest any T cell activity, since THF-treated bone marrow cells were not able to substitute thymus cells in the system used. The results accumulated in the present experiments indicate, therefore, that the target cells for THF activity are thymus cells which acquire a higher T helper cell capacity after THF treatment.

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