scholarly journals SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE

1970 ◽  
Vol 131 (2) ◽  
pp. 235-246 ◽  
Author(s):  
Harvey Cantor ◽  
Richard Asofsky
Keyword(s):  
Cell Types ◽  
Lymphoid Cells ◽  
Cell Populations ◽  
Lymphoid Tissues ◽  
Spleen Cells ◽  
F1 Hybrid ◽  
Graft Versus Host ◽  
Adult Mice ◽  
Thymus Cells ◽  
Old Mice

The capacity of cells from different lymphoid tissues obtained from Balb/c mice to produce graft-vs.-host (GVH) reactions was quantitatively determined in C57BL/6N by Balb/c F1 hybrid recipients. Synergistic responses were observed when small numbers of cells from lymphoid tissues that were rich in GVH activity such as spleen and femoral lymph node were combined with weakly reactive thymus cells. Thymus and spleen cells obtained from 1-wk old mice were separately inactive but produced moderate GVH reactions when combined in equal proportions. GVH activity of spleen cells from mice thymectomized at 3 days of age was partially restored by the addition of small numbers of spleen or thymus cells from adult mice. Changes in ratio between the two cell populations markedly affected the degree of synergy. Synergy was not observed when Balb/c cells were combined with Balb/c x C57BL/6N F1 hybrid cells and inoculated into C57BL/6N recipients, but was demonstrated when Balb/c and C57BL/6N cells were combined and inoculated into F1 recipients, indicating that a genetic disposition to mount GVH reactions in both populations is required to produce synergy. The data indicate that at least two cell types are necessary for GVH reactions, and that synergy between cell populations results from favorable adjustments in the ratio between these two cell types.

scholarly journals SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE

1970 ◽  
Vol 131 (2) ◽  
pp. 223-234 ◽  
Author(s):  
Harvey Cantor ◽  
Richard Asofsky ◽  
Norman Talal
Keyword(s):  
Host Response ◽  
Lymphoid Cells ◽  
Cell Populations ◽  
Spleen Cells ◽  
Graft Versus Host ◽  
Minimum Number ◽  
Number Of Cells

The ability of spleen cells from young (3 month) and old (1 yr) NZB mice to induce GVH reactions in newborn C57BL/6N mice was compared quantitatively using the Simonsen spleen assay. Young NZB cells were five times more reactive than cells from older mice. The minimum number of cells producing detectable reactions was 2 x 106 for the young and 10 x 106 for the old. Young and old cells combined and injected together produced GVH reactions quantitatively similar to those obtained with inocula composed of young cells alone. Mixtures of two cell populations producing no detectable reactions when injected separately into different recipients (1 x 106 young cells and 4 x 106 old cells) produced reactions approximately equal to those obtained with 5 x 106 young cells. As few as 0.25 x 106 young cells were sufficient to effect a reaction when combined with 4.75 x 106 old unreactive cells. Viability of both cell populations was essential for GVH reactivity. This evidence of synergy in GVH reactions indicates that old NZB spleen cells can be rendered immunologically more reactive in the presence of a normally reactive population.

scholarly journals Brief Report: Graft-Versus-Host Reaction in F1 Hybrid Mice Injected with Pre-Immunized Parental Thymus Cells

Blood ◽  
1964 ◽  
Vol 24 (6) ◽  
pp. 770-774 ◽  
Author(s):  
LUCIANO FIORE-DONATI ◽  
LUIGI CHIECO-BIANCHI ◽  
GIUSEPPE DE BENEDICTIS ◽  
GIUSEPPE TRIDENTE
Keyword(s):  
Lymphoid Cells ◽  
The Other ◽  
F1 Hybrids ◽  
Graft Versus Host Reaction ◽  
Host Reaction ◽  
F1 Hybrid ◽  
Graft Versus Host ◽  
Immunologic Activity ◽  
Thymus Cells ◽  
Hybrid Mice

Abstract Dissociated thymus cells are capable of initiating graft-versus-host reaction in (C3Hf/Gs x DBA/2)F1 hybrids only when derived from parental donors previously sensitized against the antigens of the other parental strain. The lower immunologic activity of thymus cells as compared with other lymphoid cells is presumably due to quantitative rather than qualitative differences in immunologically competent cells.

scholarly journals IMMUNOCOMPETENCE OF SPLEEN CELLS FROM NEONATALLY THYMECTOMIZED MICE CONFERRED IN VITRO BY A SYNGENEIC THYMUS EXTRACT

1969 ◽  
Vol 130 (4) ◽  
pp. 765-775 ◽  
Author(s):  
Nathan Trainin ◽  
Myra Small ◽  
Amiela Globerson
Keyword(s):  
Host Response ◽  
Protein Concentration ◽  
Lymphoid Cells ◽  
Immune Reactivity ◽  
Spleen Cells ◽  
Graft Versus Host ◽  
Thymus Extract ◽  
Adult Mice ◽  
Thymectomized Mice

Impaired immunological competence of spleen cells from neonatally thymectomized C57B1/6 young adult mice was apparent when these cells were tested in an in vitro graft-versus-host assay. Spleen cell inocula prepared from thymectomized mice did not induce enlargement of (C3H/eb x C57BI/6)F1 newborn spleen explants, whereas the same number of cells from intact donors consistently initiated splenomegaly. Spleen enlargement was observed, however, when the explants were challenged by cells from thymectomized donors in the presence of syngeneic thymus extract, indicating that the spleen cells in suspension attained immunological competence under the influence of a non-cellular component of the thymus. Immunocompetence was also evident when the cells from thymectomized donors were first incubated with thymus extract for 1 hr and subsequently tested for reactivity. Cells from the same thymectomized donor mice exposed in parallel to extracts from syngeneic spleen or mesenteric lymph node at an equivalent protein concentration did not initiate a graft-versus-host response. These experiments demonstrate that immune reactivity in the graft-versus-host response involves activation of lymphoid cells by a humoral factor of the thymus acting directly upon these cells.

scholarly journals STIMULATION OF ANTIBODY PRODUCTION TO THE HAPTEN 2,4-DINITROBENZENE BY AFFINITY LABELED MURINE LYMPHOID CELLS

1974 ◽  
Vol 139 (4) ◽  
pp. 943-956 ◽  
Author(s):  
David A. Lawrence ◽  
William O. Weigle
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Lymphoid Cells ◽  
Cellular Interaction ◽  
Cell Populations ◽  
Cell Contact ◽  
Spleen Cells ◽  
Normal Spleen ◽  
Thymus Cells

The ability of meta-nitrobenzenediazonium fluoborate (m-NBDF)-labeled thymus and spleen (S) cells to transfer immunity to 2,4-dinitrophenyl (DNP) into irradiated syngeneic recipients was investigated. There was a significant increase in the number of anti-DNP plaque-forming cells (PFC) when m-NBDF-labeled thymus cells and normal spleen cells, or normal thymus cells and m-NBDF-labeled spleen cells were transferred, but not when both thymus- and S-cell populations were labeled and injected together into irradiated recipients. The ability of these cell populations to cooperate and enhance the in vivo immune response to DNP is discussed. The T cells seem to be actively involved in the development of this response; they participate beyond the mere role of carrying and presenting antigen to the B cells. It is suggested that cell to cell contact between T and B cells may be an important factor in the elicitation of an immune response. In addition, the cellular interaction is affected by irradiating the thymus cell preparation and the initiating interaction required for antibody synthesis probably occurs within 48 h after injecting the cell populations into the syngeneic irradiated recipients.

scholarly journals STUDIES ON IMMUNOLOGIC RECONSTITUTION OF THYMECTOMIZED MICE

1965 ◽  
Vol 121 (4) ◽  
pp. 607-632 ◽  
Author(s):  
Edmond J. Yunis ◽  
Henry R. Hilgard ◽  
Carlos Martinez ◽  
Robert A. Good
Keyword(s):  
Intraperitoneal Administration ◽  
Lymphoid Tissues ◽  
Donor Strain ◽  
Skin Grafts ◽  
Spleen Cells ◽  
Wasting Disease ◽  
Graft Versus Host ◽  
Wasting Syndrome ◽  
Thymus Cells ◽  
Thymectomized Mice

1. Immunologic function, growth, and longevity of neonatally thymectomized mice was restored by intraperitoneal administration of 100 to 400 million syngeneic, hemiallogeneic, or ailogeneic thymus cells from newborn or adult donors. Assays of the graft versus host capabilities of spleen cells from the animals restored with allogeneic cells showed that their immunologically competent cells are of donor histocompatibility characteristics. Such animals accepted skin grafts from mice of the cell donor strain, but rejected skin from a third strain. 2. Similar results were obtained when the neonatally thymectomized animals were treated with 10 to 100 million syngeneic, hemiallogeneic, or allogeneic cells from adult spleen. 3. In one strain combination, C3H recipients and A donors, injected thymus or spleen cells apparently attacked host tissues, since the animals died very early of wasting disease. When this combination was reversed, A strain recipients treated with C3H cells were reconstituted immunologically and physiologically. 4. Syngeneic or allogeneic adult spleen, grafted in the newborn period, reconstituted neonatally thymectomized mice, but all experiments involving grafting of newborn spleen failed. Immunogenetic analysis of the host spleen cells from two allogeneic spleen-grafted animals previously thymectomized showed that the reconstitution was entirely of donor histocompatibility characteristics. 5. Postthymectomy wasting disease was reversed by administration of 200 million adult syngeneic spleen or thymus cells. Immunologic recovery was confirmed by graft versus host assays of the spleens of the recovered animals and by application of allogeneic skin grafts. Some of the animals have been under observation for 42 weeks and appear to be normal. 6. The wasting syndrome in neonatally thymectomized mice was also reversed by injection of 200 million hemiallogeneic or allogeneic spleen cells. 7. Thymus grafts did not reverse wasting disease, whether the donors were adult or newborn, of the same strain or a different one. 8. Spleen, lymph node, and Peyer's patches from representative animals of the reconstituted groups were examined and compared with the tissues of untreated neonatally thymectomized mice and intact animals of the same strain. Tissues of normal cellularity and follicular organization were found in some of the reconstituted animals and also in mice with reversed wasting disease. Extreme deficit of the lymphoid tissues was rare in either group.

scholarly journals PRODUCTION OF RUNT DISEASE IN TOLERANT MICE BY THE INJECTION OF SYNGENEIC LYMPHOID CELLS

1965 ◽  
Vol 122 (5) ◽  
pp. 1017-1027 ◽  
Author(s):  
Henry R. Hilgard ◽  
Carlos Martinez ◽  
Robert A. Good
Keyword(s):  
Weight Loss ◽  
Clinical Evidence ◽  
Rapid Onset ◽  
Lymphoid Cells ◽  
Lymphoid Tissues ◽  
Skin Grafts ◽  
Hematopoietic Tissue ◽  
Spleen Cells ◽  
F1 Hybrid ◽  
C3h Mice

When chimeric A strain mice tolerant of (A x C57BL/1)F1 hybrid skin grafts are injected with spleen cells from normal A donors the recipients develop weight loss, clinical evidence of runting, and death in some animals. Similar recipients injected with spleen cells from A strain donors immunized against C57BL/1 tissue show a more rapid onset of the runting process and increased mortality. Runting in. these experiments therefore results from an immune attack by the injected A strain lymphoid cells against the (A x C57BL/1)F1 hybrid tissue harbored by the chimeric recipients. Since the hybrid tissues of the chimeric recipients were derived from spleen cell populations we conclude that the immunologic rejection of lymphoid and hematopoietic tissue is sufficient to cause the runting syndrome. C3H mice tolerant of A strain skin grafts because of the prior injection of viable or disrupted A strain spleen material were given 400 r of x-irradiation and an injection of C3H spleen cells. Only the chimeric C3H mice harboring viable A strain cells developed weight loss and clinical evidence of disease, showing again that runting occurs only when an attack can be made against viable lymphoid and hematopoietic tissue. Normal A strain mice injected intravenously with 850 million (A x C57BL/1)F1 hybrid spleen cells reject hybrid skin grafts and do not develop runting, whereas the rejection of similar hybrid tissue present in chimeric A strain mice results in runting. It is concluded that runting will occur only when the immunologic attack is directed against lymphoid and hematopoietic tissue which has become established within host tissues. The possibility that runting may result from hypersensitivity reactions occurring in the lymphoid tissues is discussed.

scholarly journals SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE

1973 ◽  
Vol 137 (2) ◽  
pp. 239-253 ◽  
Author(s):  
Robert E. Tigelaar ◽  
Richard Asofsky
Keyword(s):  
Normal Population ◽  
Lymphoid Cells ◽  
Spleen Weight ◽  
Spleen Cells ◽  
Parent Population ◽  
Graft Versus Host ◽  
Adult Mice ◽  
Peripheral Lymph ◽  
Normal Expression

Spleen cells from normal adult mice were injected into lethally irradiated adult syngeneic recipients. 24 h later, cell suspensions were prepared from the recipients' spleens or peripheral lymph nodes and tested either alone or combined for their capacity to elicit graft-versus-host (GVH) reactions in neonatal F1 recipients, using the Simonsen spleen weight assay. Either the lymph node-seeking subpopulation or the spleen-seeking subpopulation alone was markedly deficient in its ability to provide a GVH reaction when compared with the normal population from which it was derived. However, an appropriate mixture of the two had a reactivity characteristic of the parent population. Both subpopulations were sensitive to treatment with anti-θ antibody and complement in vitro. These results provide a convincing demonstration of the functional heterogeneity within the pool of thymus-derived cells present in a single normal lymphoid tissue. They strongly suggest that the normal expression of GVH reactivity of such a tissue involves an interaction among distinct subpopulations of thymus-derived cells.

scholarly journals STUDIES ON THE ROLE OF THE THYMUS IN IMMUNOBIOLOGY

1963 ◽  
Vol 118 (6) ◽  
pp. 1089-1109 ◽  
Author(s):  
Agustin P. Dalmasso ◽  
Carlos Martinez ◽  
Kenneth Sjodin ◽  
Robert A. Good
Keyword(s):  
Lymphoid Tissues ◽  
Donor Strain ◽  
Skin Grafts ◽  
Spleen Cells ◽  
Thymic Tissue ◽  
Graft Versus Host ◽  
Thymus Tissue ◽  
C57bl Mice ◽  
Thymus Cells ◽  
Thymectomized Mice

The immunologic competence of spleen cells of mice, as assessed by their graft versus host capabilities, increases to 35 days of age and beyond. Thymectomy at any point along this continuum of development produces "immunologic arrest;" the peripheral lymphoid tissues of such mice do not show significant increases in activity as the animals mature, nor is there appreciable loss of activity up to 6 months after surgery. Adult spleen cells from mice thymectomized at 1 to 24 hours of age have a greatly reduced ability to induce runt disease. Five million spleen cells from immunologically mature animals will uniformly cause fatal runt disease in neonatal recipients, but this same number of cells from neonatally thymectomized animals produces almost no runt disease. When the dosage of cells from neonatally thymectomized C57Bl mice is increased to 20 million, about half of the A recipients develop runt disease. Thus, the defect is a quantitative one. Spleen cells from neonatally thymectomized mice will induce tolerance of skin grafts from the donor strain. In one recalcitrant strain combination, C57Bl to A, use of spleen cells from neonatally thymectomized donors as the tolerance-inducing inoculum permits survival of the recipients, which usually die with severe runt disease, but does not induce tolerance. Cell free extracts of spleen and thymus tissue, including "promine" of Szent-Gyorgyi et al., did not affect the runting syndrome or the immunologic reactivity of neonatally thymectomized mice. When syngeneic thymic tissue is grafted into neonatally thymectomized mice, or the animals are given viable syngeneic spleen or thymus cells, the majority of the animals escape the early mortality characteristic of this group. Administration of syngeneic spleen cells from adult donors and grafting of syngeneic neonatal thymus provide restoration of homograft immunity and graft versus host reactivity of the peripheral lymphoid tissues in most of the neonatally thymectomized animals. Thymus cells rarely provide significant restoration of these parameters. Allogeneic thymus grafts also restore neonatally thymectomized mice. Such animals are chimeric: the immunologically competent cells of their peripheral lymphoid tissues are chiefly of host origin as determined by the discriminant spleen assay, but in many instances a significant donor component is also demonstrable in this system. These chimeric animals accept skin grafts from both donor and host strains. A degree of reconstitution has also been attained by grafting of allogeneic adult spleen in neonatally thymectomized animals. The discriminant spleen assay indicates that cells of the donor strain predominate in the peripheral lymphoid tissues of such mice.

scholarly journals Study of the cells proliferating in parent versus F hybrid mixed lymphocyte culture.

1975 ◽  
Vol 141 (4) ◽  
pp. 775-787 ◽  
Author(s):  
P F Piguet ◽  
H K Dewey ◽  
P Vassalli
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Lymphocytes ◽  
Hybrid Cell ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Lymphoid Cells ◽  
Spleen Cells ◽  
F1 Hybrid ◽  
Proliferation And Differentiation

Caryotypic analysis of the cells dividing in mouse parent-hybrid MLC showed an F1 hybrid cell proliferation, which varied depending upon the source of lymphoid cells used: strong in spleen MLC (sometimes equal to that of the parental cells), less marked in lymph node cell MLC, and most often absent in MLC between cortisone-resistant (CR) thymocytes. MLC between parental spleen cells and F1 CR thymocytes showed, however, that in certain conditions of culture F thymocytes can also proliferate. Using parental or F1 spleen cells lacking T lymphocytes, it was found that F1 cell proliferation is entirely dependent upon the presence of parental T cells, but does not require the presence of T lymphocytes among the F1 cells. Immunofluorescence analysis of the blasts observed in one-way MLC showed that about 70% of the parental blasts were T blasts, and 25%B blasts (containing a high proportion of plasmablasts); among the F1 blasts, there was also the same percentage of B blasts and plasmablasts, but many of the T blasts bore only small amounts of T-cell antigen (MTLA), and there was also about 20%of unstained blasts, possibly T blasts bearing MTLA in amounts undetectable by immunofluorescence. The possibility is discussed that the F1 responding T cells belong to a subpopulation performing a suppressive function; MLC lacking F1 T cells showed increased [3H] thymidine incorporation. The proliferation and differentiation of parental and F1 B cells may result mainly from an unspecific, "polyclonal" triggering.

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