Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By induction of a graft-vs.-host reaction (GVHR) in nonirradiated H-2-different F1 mice, one can induce stimulatory pathological symptoms, such as lymphadenopathy and hypergammaglobulinemia, combined with the production of autoantibodies characteristic of systemic lupus erythematosus (SLE). Alternatively, the GVHR can lead to the suppressive pathological symptoms, such as pancytopenia and hypogammaglobulinemia, characteristic of acute GVH disease (GVHD). Whether stimulatory or suppressive symptoms are induced by a GVHR depends, in our view (2-4), on the functional subset of donor T cells activated in the F1 host. The purpose of the present study was to investigate whether class I and/or class II H-2 alloantigens can selectively trigger, out of a pool of unselected donor T cells, those subpopulations of T cells responsible for the stimulatory and suppressive GVH symptoms, respectively. For the induction of the GVHR, 10(8) lymphoid cells from C57BL/6 (B6) donors were injected into three kinds of F1 hybrid mice, which had been bred from H-2 mutant strains on a B6 background. Whereas the I-A-disparate (B6 X bm12)F1 recipients exclusively developed stimulatory GVH symptoms, including SLE-like autoantibodies and immune complex glomerulonephritis, the K locus-disparate (B6 X bm1)F1 recipients showed neither clearly stimulatory nor clearly suppressive GVH symptoms. In marked contrast, the (bm1 X bm12)F1 recipients, which differ from the B6 donor strain by mutations at both K and I-A locus, initially developed stimulatory GVH symptoms, but rapidly thereafter showed the suppressive pathological symptoms of acute GVHD and died. Moreover, spleen cells obtained from (B6 X bm12)F1 mice injected with B6 donor cells helped the primary anti-sheep erythrocyte (SRBC) response of normal (B6 X bm12)F1 spleen cells in vitro, whereas spleen cells (bm1 X bm12)F1 mice injected with B6 donor cells strongly suppressed the primary anti-SRBC response of normal (bm1 X bm12)F1 spleen cells. Spleen cells from the K locus-disparate (B6 X bm1)F1 recipients also suppressed the primary anti-SRBC of normal (B6 X bm1)F1 spleen cells; this suppression, however, was weak when compared with the suppression induced by spleen cells from GVH (bm1 X bm12)F1 mice. Taken together, these findings indicate that a small class II (I-A) antigenic difference suffices to trigger the alloreactive donor T helper cells causing SLE-like GVHD. In contrast, both class I (H-2K) and class II (I-A) differences are required to trigger the subsets of donor T cells responsible for acute GVHD. It appears that alloreactive donor T helper cells induce the alloreactive T suppressor cells, which then act as the suppressor effector cells causing the pancytopenia of acute GVHD. These findings may help to understand the variability of GVH-like diseases caused by a given etiologic agent, their cellular pathogenesis, and association with certain HLA loci.
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PMID:Allosuppressor and allohelper T cells in acute and chronic graft-vs.-host disease. II. F1 recipients carrying mutations at H-2K and/or I-A. 621 18

Lethally irradiated mice were transplanted with bone marrow plus spleen cells from H-2 identical donor mice. Five of the six recipient strains developed lethal GVHD, but the sixth strain did not develop any signs of GVHD. Spleen cells from all six transplanted strains were cytotoxic to recipient strain target cells in a short-term chromium release assay. The cytotoxic spleen cells were antigen-specific for recipient strain target cells, Thy-1+ and Lyt-2+--and some were also Lyt-1+. These data demonstrate for the first time that the presence of antirecipient cytotoxic T lymphocytes (CTL) does not correlate with lethal GVHD. Although CTL may contribute to the pathogenesis of GVHD in response to minor histocompatibility antigens, they do not appear to be the primary effector mechanism.
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PMID:Absence of correlation between cytolytic T lymphocytes and lethal murine graft-versus-host disease in response to minor histocompatibility antigens. 638 62

A model for bone marrow transplantation across minor histocompatibility barriers was developed by using mouse strains that were H-2 identical and mutually non-reactive in MLC. Acute graft-vs-host disease was induced only when donor lymphoid cells were included in the marrow inoculum, in both C57BL/6 recipients of LP cells and BALB/c recipients of B10.D2/nSN cells. GVHD was prevented by treating the lymphoid cells with anti-Thy 1.2 and C before transplantation. Spleen cells from mice with acute GVHD were not directly cytotoxic to recipient strain target cells. However, when spleen cells from mice with GVHD were boosted in vitro to recipient strain stimulator cells they generated a specific anti-recipient cytotoxic response. Spleen cells from mice without GVHD did not generate a cytotoxic response in vitro. The cytotoxic effector cells and their precursors were shown to be T lymphocytes. This model and the in vitro method described may be useful in further studies of the immunobiology of GVHD due to minor histocompatibility antigens and of transplantation tolerance.
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PMID:Anti-recipient cytotoxic T lymphocyte precursors are present in the spleens of mice with acute graft versus host disease due to minor histocompatibility antigens. 645 Feb 46

The immune reactivity of lymphoid cells from pregnant mice was studied during the course of pregnancy in primiparous and multiparous animals either " isopregnant " (male and female of same strain) or " allopregnant " (male and female differing at H-2), using a local GVH assay (CBA lymphoid cells injected into (CBA X A/J)F1 recipients). The findings were as follows: The lymphoid cell number in the para-aortic lymph nodes ( PALN ) was increased at all stages of gestation. The peak occurred in the 2nd week in primiparity and as early as 60 h after fertilization in multiparity. PALN cell alloreactivity was weak at the beginning and higher than normal in the third week of pregnancy. Spleen cell alloreactivity was increased in the second week and decreased in the third week in primiparous compared with multiparous animals. Anti-paternal alloreactivity exhibited by spleen cells of allogestation was decreased (as compared to cells of isogestation ) especially in primiparous mice, particularly in the third week. At this time, the anti-paternal alloreactivity of PALN cells was increased. The influence of the recipient's sex on GVHR intensity was reversed when the cells were obtained from a pregnant donor, becoming stronger in male compared with female hybrids.
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PMID:Allogeneic reactivity of maternal lymphoid cells during the course of gestation. Modifications and sex differences in a local GVH assay. 673 70

Spleen cells from (C57BL/10 x B10.A)F1 mice that had been injected 2 wk earlier with C57BL/10 (B10) or B10.A parental spleen cells were mixed with spleen cells from untreated F1 mice. The cell mixture was sensitized in vitro to trinitrophenyl-modified syngeneic cells (TNP-self) or alloantigens for a cell-mediated lympholysis (CML) response, and assayed for effector cell activity 5 days later. Cells from B10.A- but not B10-injected F1 spleens suppressed the CML of normal F1 spleens cells. In contrast, strong suppressive activity was obtained from irradiated B10-injected F1 mice. Thus, F1 mice were selectively resistant to GVH-associated immunosuppression induced by B10, but not by B10.A, parental spleen cells, and this F1 resistance mechanism appeared to be radiosensitive. The suppressive activity of spleen cells from irradiated, parental-injected F1 mice could be at least partially accounted for by cytotoxic activity of parental cells directed against alloantigens expressed by the F1. However, suppressor activity in intact parental-injected F1 mice appeared to be due to parental-induced F1 suppressor cells. The results are discussed with respect to: a) the use of this system as a possible model for investigating the selective resistance of F1 mice to parental T cell-induced GVH reactions, and b) the implications involved in the mutual recognition between F1 and parental lymphocytes, which may be relevant for immune surveillance against self-reactive T cell clones.
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PMID:Mutual recognition of parental and F1 lymphocytes. II. Analysis of graft-vs-host-induced suppressor cell activity for T cell-mediated lympholysis to trinitrophenyl self and alloantigens. 696 20

Spleen cells from 14-month-old mice are capable to induce GVH reaction in syngeneic recipients. Spleen cells obtained on the third day after hydrocortisone injection also induce GVH reaction in syngeneic recipients. The results suggest that T cells which suppress the activity of autoreactive lymphocytes are eliminated with age and after exposure to hydrocortisone.
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PMID:[Autoreactivity of splenic cells of old rats and animals treated with hydrocortisone]. 697 17

Four hundred and ten heterotopic spleen transplants were performed in inbred guinea pigs of strains 2 and 13 whose major histocompatibility complex differs only in the I region and which rapidly reject reciprocal skin allografts. Spleen allografts from strain 13 to strain 2 survived throughout the lifetime of the hosts, whereas spleen allografts from strain 2 to strain 13 were rejected within 3 weeks. Animals not rejecting their spleen transplants were specifically tolerant of donor strain skin allografts. Strain 2 recipients of strain 13 spleen grafts had a surprising high mortality from graft-versus-host disease which peaked at 6 weeks after transplantation.
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PMID:Induction of transplantation tolerance in guinea pigs by spleen allografts. I. Operative techniques and clinical results. 703 23

In a fully MHC plus multiple minor antigen-mismatched murine bone marrow transplantation (BMT) model, we have demonstrated that a short course of high dose IL-2, begun on the day of BMT, protects against graft-versus-host disease (GVHD). This inhibitory effect is directed against donor CD4+ cells. To determine whether the mechanism of IL-2-induced GVHD protection involves clonal deletion or anergy of host-reactive donor T helper cells (Th), we performed limiting dilution analyses to measure the frequency of activated Th that reacted to donor, host, and third-party antigens in GVHD control and IL-2-protected mice. Marked and specific expansion of host-reactive Th was observed to a similar extent in GVHD control and IL-2-protected mice by day 5 after BMT, and the number of these cells in the spleen increased by several orders of magnitude between days 3 and 5 after BMT, which suggests that recirculation from other tissues occurred in this period. A high proportion (approximately 80%) of donor T cells expressed CD25 in both GVHD control and IL-2-protected mice on day 4 after BMT, which suggests a high level of bystander T cell activation. Since marked quantitative differences in the GVH response were not observed between GVHD control and IL-2-protected mice, we assessed both groups for qualitative differences in the Th response. Spleen cells isolated in the first 8 days after BMT were cultured with host-type, donor-type, or third-party stimulators or without stimulators, and cytokines were measured in supernatants harvested at 24 hr. GVHD was associated with marked increases in supernatant IFN-gamma levels from day 3 to day 6 after BMT, and with increases in IL-2 levels compared with naive A/J controls or syngeneic BMT controls stimulated with host antigens. Production of these cytokines was specifically induced by host-type antigens. Supernatants from spleens of IL-2-treated mice showed delayed kinetics of IFN-gamma production, and tended to contain higher levels of IL-4 in response to host antigen compared with GVHD controls on days 2 and 4 after BMT. Both IL-4 and IFN-gamma were produced almost exclusively by CD4+ cells in spleens of GVHD control and IL-2-protected mice on day 4. However, no consistent difference was observed between the groups in supernatant IL-2 or IL-10 levels, ruling out a simple Th1 to Th2 switch.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Inhibition of graft-versus-host disease by interleukin-2 treatment is associated with altered cytokine production by expanded graft-versus-host-reactive CD4+ helper cells. 767 98

Graft-versus-host disease (GVHD) due to allogeneic bone marrow transplantation can be prevented by depleting the T cells from the marrow graft in vitro. However, the elimination of the donor T cells results in a higher frequency of graft failure, secondary infections and, in case of leukaemia, relapse. We found, that, in contrast to normal spleen cells, spleen cells from A or B10 donor mice pretreated with xenogeneic antithymocyte serum (ATS) in vivo did not induce GVHD in non-irradiated (B10 x A)F1 hybrids. Spleen cells of ATS-pretreated A donors did not cause GVHD in allogeneic CBA mice made neonatally tolerant to the A donor strain either. Furthermore, spleen cells from ATS-treated donors did not cause GVHD in irradiated F1 hybrid recipients, moreover, they decreased the lethal effect of irradiation. The in vivo ATS pretreatment improved the repopulating capacity of spleen cells in irradiated syngeneic recipients, too. The effect of the ATS treatment does not rely solely upon the elimination of T cells, since flow cytofluorometric analysis revealed only a partial depletion of both the CD4+ and CD8+ T cells of the ATS-pretreated animals. These observations may also have clinical relevance.
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PMID:Spleen cells from antithymocyte serum pretreated mice do not induce GVHD but exert increased repopulating activity in irradiated semiallogeneic recipients. 787 94

Spleen cells from mice infected with LP-BM5 MuLV, a causative agent of murine acquired immunodeficiency syndrome (MAIDS), were tested for frequency of NK-1.1+ cells and natural killer (NK) activity. During the first 3 weeks following infection, NK activity was well conserved, but by 9-12 weeks post-infection (p.i.), killer activity was depressed; however, the frequency of NK-1.1+ cells increased within 4 weeks of infection and remained elevated thereafter, even following the decline in functional killing activity. Since the absolute number of NK-1.1+ cells increased after infection, the ability of each NK-1.1+ cell to kill the targets seems drastically impaired. Extraordinary expansion of NK-1.1-positive cells was induced by infection with LP-BM5-defective virus (BM5def), a crucial element for MAIDS induction, but not with a helper non-pathogenic virus. With advance of MAIDS the NK-1.1 antigen (Ag) was preferentially expressed on B220+ and Thy-1+ cells, in contrast to CD4+ and CD8+ cells, and among activated large cells a higher proportion was NK-1.1+ than NK-1.1-. Mice with graft-versus-host disease (GVHD) due to class II major histocompatibility complex (MHC) Ag disparity showed a high frequency of NK-1.1 expression in association with other phenotypic alterations, very similar to those seen in mice with MAIDS. In contrast, B6-lpr/lpr mice developed similar activation of B cells but did not exhibit enhanced expression of the NK-1.1 marker. Thus, enhanced expression of the NK-1.1 Ag might be associated with chronic activation of lymphocytes through a common but not universal pathway.
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PMID:High expression of NK-1.1 antigen is induced by infection with murine AIDS virus. 826 61


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