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

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 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.

scholarly journals Positive Selection of γδ CTL by TL Antigen Expressed in the Thymus

1996 ◽  
Vol 184 (6) ◽  
pp. 2175-2184 ◽  
Author(s):  
Kunio Tsujimura ◽  
Toshitada Takahashi ◽  
Akimichi Morita ◽  
Hitomi Hasegawa-Nishiwaki ◽  
Shigeru Iwase ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Positive Selection ◽  
Transgenic Mouse ◽  
Mouse Strains ◽  
Skin Grafts ◽  
Spleen Cells ◽  
C3h Mice ◽  
Ctl Activity ◽  
Selection Of

To elucidate the function of the mouse TL antigen in the thymus, we have derived two TL transgenic mouse strains by introducing Tlaa-3 of A strain origin with its own promoter onto a C3H background with no expression of TL in the thymus. These transgenic mouse strains, both of which express high levels of Tlaa-3-TL antigen in their thymus, were analyzed for their T cell function with emphasis on cytotoxic T lymphocyte (CTL) generation. A T cell response against TL was induced in Tg.Tlaa-3-1, Tg.Tlaa-3-2, and control C3H mice by skin grafts from H-2Kb/T3b transgenic mice, Tg.Con.3-1, expressing T3b-TL ubiquitously. Spleen cells from mice that had rejected the T3b-TL positive skin grafts were restimulated in vitro with Tg.Con.3-1 irradiated spleen cells. In mixed lymphocyte cultures (MLC), approximately 20% and 15% of Thy-1+ T cells derived from Tg.Tlaa-3-1 and Tg.Tlaa-3-2, respectively, expressed TCRγδ, whereas almost all those from C3H expressed TCRαβ. The MLC from Tg.Tlaa-3-2 and C3H demonstrated high CTL activity against TL, while those from Tg.Tlaa-3-1 had little or none. The generation of γδ CTL recognizing TL in Tg.Tlaa-3-2, but not C3H mice, was confirmed by the establishment of CTL clones. A total of 14 γδ CTL clones were established from Tg.Tlaa-3-2, whereas none were obtained from C3H. Of the 14 γδ CTL clones, 8 were CD8+ and 6 were CD4−CD8− double negative. The CTL activity of all these clones was TL specific and inhibited by anti-TL, but not by anti-H-2 antibodies, demonstrating that they recognize TL directly without antigen presentation by H-2. The CTL activity was blocked by antibodies to TCRγδ and CD3, and also by antibodies to CD8α and CD8β in CD8+ clones, showing that the activity was mediated by TCRγδ and coreceptors. The thymic origin of these γδ CTL clones was indicated by the expression of Thy-1 and Ly-1 (CD5), and also CD8αβ heterodimers in CD8+ clones on their surfaces and by the usage of TCR Vγ4 chains in 12 of the 14 clones. Taken together, these results suggest that Tlaa-3-TL antigen expressed in the thymus engages in positive selection of a sizable population of γδ T cells.

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 Oxidative Stress Produced by Hyperthyroidism Status Induces the Antioxidant Enzyme Transcription through the Activation of the Nrf-2 Factor in Lymphoid Tissues of Balb/c Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Melisa Costilla ◽  
Rodrigo Macri Delbono ◽  
Alicia Klecha ◽  
Graciela Alicia Cremaschi ◽  
María Laura Barreiro Arcos
Keyword(s):  
Lymph Node ◽  
Thyroid Hormones ◽  
Antioxidant Enzyme ◽  
Energy Demand ◽  
Lymphoid Cells ◽  
Lymphoid Tissues ◽  
Related Factor ◽  
Spleen Cells ◽  
Excessive Secretion

Hyperthyroidism is an endocrine disorder characterized by excessive secretion of thyroid hormones T3 and T4. Thyroid hormones exert pleiotropic actions on numerous tissues and induce an overall increase in metabolism, with an increase in energy demand and oxygen consumption. Therefore, the purpose of this study was to investigate the effects of hyperthyroidism on the production of reactive oxygen species (ROS) in lymph node and spleen cells of euthyroid and hyperthyroid mice, analyzing antioxidant mechanisms involved in the restitution of the cellular redox state. For this, thirty female Balb/c (H-2d) mice were randomly divided into two groups: euthyroid (by treatment with placebo) and hyperthyroid (by treatment with 12 mg/l of T4 in drinking water for 30 days). We found a significant increase in ROS and an increase in the genomic and protein expression of the antioxidant enzymes catalase (CAT) and glutathione peroxidase-1 (GPx-1) in lymph node and spleen cells of hyperthyroid mice. In vitro treatment with H2O2 (250 μM) of the lymphoid cells of euthyroid mice increased the expression levels of CAT and GPx-1. The hyperthyroidism increased the phosphorylation levels of Nrf2 (nuclear factor erythroid 2-related factor) and the kinase activity of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK). Additionally, we found an increase in the expression of the classic isoenzymes of PKCα, β and γ. In conclusion, these results indicated that the increase in ROS found in the hyperthyroid state induces the antioxidant enzyme transcription through the activation of the Nrf-2 factor in lymphoid tissues. This shows the influence of hyperthyroidism on the regulation of the cellular antioxidant system.

scholarly journals ACQUIRED TOLERANCE TO SKIN HOMOGRAFTS IN MICE

1963 ◽  
Vol 117 (3) ◽  
pp. 543-560 ◽  
Author(s):  
Bertie F. Argyris
Keyword(s):  
Immune Response ◽  
Lymph Nodes ◽  
Graft Rejection ◽  
Lymphoid Cells ◽  
Axillary Lymph Nodes ◽  
Lymphoid Tissues ◽  
Axillary Lymph ◽  
C3h Mice ◽  
Immune Potential ◽  
Graft Reaction

Acquired tolerance to CBA skin homografts is lost in a large number of C3H mice neonatally injected with CBA spleen cells. The skin homografts persist for at least 2 months but then exhibit a chronic rejection pattern which may last up to 7 months. Histological analysis of the lymphoid tissues reveals the onset of an immune response in the axillary lymph nodes of many 4-month-old tolerant mice. This immune response which appears before external indications of graft rejection are evident, is manifested as an increase in number of germinal centers and plasma cells in the cortex and medulla, respectively. In older tolerant mice, an even larger proportion show these histological indications of immunological activity. During graft contraction and shortly after graft rejection, the immune response is still limited to the lymph nodes. After rejection of a second graft by post-tolerant mice, histological indications of an immune response are not only found in lymph nodes but also in spleen. The data suggest the development of a host versus graft reaction in seemingly tolerant C3H mice, which increases in severity with the age of the animal. The results are discussed from the point of view that tolerance is dependent upon a critical balance between the immune potential of the host and the population of donor cells. As mice mature, their immune potential may increase. The resulting host versus graft reaction increases, culminating in the rejection of skin graft and donor lymphoid 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.

Transfer of donor immunological reactivity to x-irradiated F1 hybrid mice by injected parental bone marrow

1958 ◽  
Vol 196 (1) ◽  
pp. 100-104
Author(s):  
L. J. Cole ◽  
R. M. Garver ◽  
M. E. Ellis
Keyword(s):  
Bone Marrow ◽  
Protective Effect ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Test System ◽  
Lymphoid Cells ◽  
X Rays ◽  
Spleen Cells ◽  
F1 Hybrid ◽  
Marrow Cells

Mice of the (LxA)F1 strain were exposed to an ld100 dose of x-rays (870 r), and injected with bone marrow cell suspensions from A-strain mice. Excellent protection against death was observed during the first 3 weeks, followed by secondary ‘homologous’ deaths during the ensuing weeks. When A-strain (parental strain) spleen cells were injected, together with A-strain bone marrow, the protective effect was annulled. When A-spleen cells were injected together with LAF1 bone marrow cells into irradiated LAF1 mice, again no protection was observed. However, injected LAF1 spleen cells did not influence adversely the course of protection of x-irradiated A-strain mice by injected A-bone marrow. The findings formed the basis for an experimental test system for detecting the presence of A-lymphoid cells in the tissues of irradiated LAF1 mice which had been injected with A-bone marrow. The data indicate that the spleen and thymus of LAF1 mice 21 days after irradiation and injection of A-marrow contain A-lymphoid cells which when injected, in turn, into irradiated LAF1 mice treated with LAF1 marrow, annuls the protective effect of the injected marrow. It is concluded that a reaction (of an immunological nature) of the injected bone marrow cells, or their progeny, against the host tissues, contributes to the phenomenon of the late deaths. The significance of these results with respect to the problem of ‘homologous disease’ in lethally x-irradiated mice treated with homologous bone marrow, has been discussed.

scholarly journals IMMUNOLOGIC INCOMPETENCE OF IMMUNOLOGICALLY RUNTED ANIMALS

1964 ◽  
Vol 119 (2) ◽  
pp. 211-224 ◽  
Author(s):  
R. Michael Blaese ◽  
Carlos Martinez ◽  
Robert A. Good
Keyword(s):  
Parent Strain ◽  
Neonatal Period ◽  
Lymphoid Cells ◽  
F1 Hybrids ◽  
Graft Versus Host Reaction ◽  
Spleen Cells ◽  
Host Reaction ◽  
Graft Versus Host ◽  
Donor Cells ◽  
C3h Mice

1. Adult (A x C57Bl/1)F1 hybrids regularly show runt disease when injected with adult spleen cells from A strain donors. This also occurs when A strain spleen cells are administered to adult C3H mice made tolerant of A strain tissue in the neonatal period. 2. Mice undergoing the graft versus host reaction fail to form antibodies to an intraperitoneal challenge of T2 bacteriophage. This phenomenon was observed well before any of the other overt signs of runting had occurred. Further, inhibition of antibody production to T2 phage by graft versus host reaction initiated at an interval following antigenic stimulation is demonstrated. 3. The basis for the immunologic incompetence of the host with respect to T2 phage is presumed to be the attack of immunologically competent donor cells on the lymphoid cells of the recipient. 4. The failure of the injected parent strain cells to respond to the antigen used may imply immunologic commitment of these cells.

scholarly journals Induction of long-term H-Y-specific tolerance in female mice given male lymphoid cells while transiently depleted of CD4+ or CD8+ T cells.

1993 ◽  
Vol 177 (6) ◽  
pp. 1587-1592 ◽  
Author(s):  
F P VanderVegt ◽  
L L Johnson
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Lymphoid Cells ◽  
Transplantation Antigen ◽  
Skin Grafts ◽  
Cd4 Cells ◽  
Spleen Cells ◽  
Cd8 Cells ◽  
Female Mice

Rejection of H-Y-bearing primary skin grafts and generation of H-Y-specific cytolytic T cells by female mice requires the participation of both CD4+ and CD8+ T lymphocytes. Studies were conducted to investigate long-term tolerance of H-Y antigen induced in female mice by transiently depleting them of CD4+ and/or CD8+ T cells and, at the same time, giving them an injection of male lymphoid cells. We confirmed that after recovery of CD4+ to normal levels, female mice that had been transiently depleted of CD4+ cells and concurrently given an injection of male spleen cells were unable to generate H-Y-specific cytolytic T cells. Tolerance was also manifest by greatly extended survival (probably permanent in most cases) of male skin grafts. Further investigations revealed that female mice transiently depleted of CD8+ cells, and concurrently given an injection of male spleen cells, were similarly tolerant of H-Y antigen later when numbers of CD8+ T cells returned to normal. Moreover, small numbers of male cells were detectable in spleen and lymph nodes of tolerant females long after they had been given an injection of male cells and depleted of either CD4+ or CD8+ T cells, whereas no male cells were detected in (nontolerant) females given male cells and control antibodies. These findings show that tolerance of the relatively weak transplantation antigen, H-Y, can be achieved simply by giving male antigen-bearing spleen cells to the host while it is transiently depleted of a type of cell it needs in order to reject those cells, thus allowing the male cells to persist in the host. Furthermore, depletion of helper cells is not obligatory to achieve tolerance. It has been hypothesized that tolerance of H-Y antigen in females given male lymphoid cells while temporarily depleted of CD4+ lymphocytes results from unresponsiveness (anergy) induced in H-Y-specific CD8+ cells that are exposed to H-Y antigen in the absence of help from CD4+ cells. Interpretations of our findings are discussed in relation to this hypothesis.

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