Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In two H-2b anti-H-2d but not in H-2b anti-H2k donor-recipient combinations, graft-versus-host reaction (GVHR) mortality was found to vary as a function of the host's genetic background; the same non-major histocompatibility complex genes and/or antigens which influence GVHR mortality do not influence the intensity of GVHR splenomegaly or the time of skin rejection. In contrast, the severity of GVHR mortality correlates with the intensity of stimulation in mixed lymphocyte culture. The roles of minor histocompatibility (H) antigens and Mls product are discussed.
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PMID:Graft-versus-host reaction. Influence of genetic background in donor-recipient pairs incompatible for major histocompatibility complex (MHC). 1 21

This study investigated the hypothesis that sensitivity to L-leucyl-leucine-methyl ester (Leu-leu-O-Me) can be used to identify a role for cytotoxic lymphocytes in alloreactivity. Treatment of donor lymphocytes with Leu-leu-O-Me profoundly inhibited their ability to induce three separate models of murine graft-versus-host reaction (GVHR). This was observed for all aspects of GVHR examined, including weight loss, splenomegaly and activation of natural killer (NK) cells. These effects were not influenced by whether specific cytotoxic T lymphocytes (CTL) were involved in individual models of GVHR. Leu-leu-O-Me not only eliminated NK and CTL activity in vitro, but had identical effects on the proliferation of T and B lymphocytes in response to a variety of mitogenic stimuli. Finally, Leu-leu-O-Me prevented immune lymphocytes from mediating both class I and class II major histocompatibility complex (MHC)-restricted delayed-type hypersensitivity (DTH) responses in vivo. It is concluded that Leu-leu-O-Me has non-specific toxicity for most lymphocyte function and that it cannot be used as a specific means of predicting the functional roles of CTL.
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PMID:Generalized toxicity of L-leucyl-leucine-methyl ester for lymphocyte functions. 233 75

Determinations of 50% lethal dose (LD50) values in H-2 congenic B10 lines showed that late-emerging resistance (postimmune response phase) to salmonellae of intermediate virulence was less in H-2b and H-2d than in H-2a, H-2k, and H-2f mice. Association of resistance to H-2 was confirmed by backcross analysis, and LD50 determinations on H-2 recombinant haplotype strains showed that resistance maps to the I-E subregion. Bacterial growth curves in liver and spleen showed that susceptible mice carried bacteria for longer in the reticuloendothelial system than did resistant mice and that susceptible mice showed greater splenomegaly. Association of resistance and susceptibility to H-2 was not different when sister transductant salmonellae expressing somatic antigens O4 and O9 were used. Thus a gene(s) within the major histocompatibility complex controls natural resistance to salmonellae in mice by influencing the ability to clear bacteria from the reticuloendothelial system in the later phase of the infection, and the immunodominant O antigen cannot be solely involved.
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PMID:Natural resistance to salmonellae in mice: control by genes within the major histocompatibility complex. 241 42

B cells from bursa of Fabricius of newly hatched chickens are able to reconstitute the B cell compartment of chemically bursectomized chickens. The resulting B cell chimerism can be detected with monoclonal antibodies against donor B cell alloantigen. Chimeric chickens accept donor-type skin grafts and are unresponsive to donor major histocompatibility complex (MHC) antigens in graft-vs.-host splenomegaly assay and mixed lymphocyte reaction. To study the capability of B cells to induce tolerance to selected MHC antigens, we transplanted class I or total MHC-incompatible bursa cells into cyclophosphamide-treated recipients. The recipients of class I or total MHC-incompatible bursa cells were equally tolerant of donor-MHC antigens. To further analyze the mechanisms of tolerance to class I antigens vs. total MHC, spleen cells from tolerant chickens were transferred to irradiated, histocompatible secondary hosts. The secondary recipients were also unresponsive to bursa cell donor-strain MHC antigens. However, if the chimeric B cells were depleted before the spleen cell transfer, the transfer of tolerance to total MHC was severely inhibited. Instead, most recipients of B cell-depleted spleen cells tolerant of class I antigens were still tolerant of bursa cell donor MHC. Our results indicate differences in the transferability of tolerance to class I antigens vs. entire MHC, although in primary recipients of bursa cells the tolerance is similar. These data suggest that a mechanism that is not dependent on the presence of donor cell chimerism contributes to the maintenance of tolerance to donor class I antigens. The transfer of tolerance to total MHC disparity requires the presence of chimeric cells indicating that donor alloantigen expression is needed for induction of tolerance in the secondary hosts.
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PMID:Tolerance to class I major histocompatibility complex antigens in chicken B cell chimeras. Effect of B cell depletion on transferability of tolerance. 252 10

Transplantation of cells from the bursa of Fabricius reconstitutes the B cell system of chemically bursectomized chickens. Even allogeneic bursa cells can restore the recipient's B cell system and induce tolerance to donor major histocompatibility complex antigens, but the chimeras cannot mount a T-dependent antibody response. In order to study the mechanisms of tolerance to class II MHC (B-L) antigens, we transplanted class II-incompatible bursa cells from 4-day-old donors into cyclophosphamide-treated recipients of the same age. Donor and host cells carried different allelic products of a genetically polymorphic B cell alloantigen (Bu-1), allowing us to detect cellular chimerism using monoclonal antibodies and immunofluorescence. The B cell-chimeric chickens were tested for tolerance by skin grafting, graft-versus-host splenomegaly assay, and mixed lymphocyte reaction. Specific unresponsiveness to donor MHC antigens was observed in all three tests. When spleen cells from chickens tolerant of donor class II antigens were transferred into irradiated secondary recipients of the same strain, several of the secondary recipients accepted primary donor-type skin grafts. Most secondary recipients were, however, reactive in the GVH assay and MLR. Depletion of chimeric B cells before spleen cell transfer impaired the transferability of tolerance to class II disparity. Altogether, our results indicate that tolerance to class II antigens can be induced with B cells. They suggest that at least two different mechanisms maintain the unresponsiveness in B cell-chimeric chickens.
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PMID:B cell-induced tolerance to class II MHC antigens in the chicken. 252 81

Implantation of either major histocompatibility complex (MHC)-disparate thymus to 7-day thymectomized (Tx) Xenopus in late larval life, or allogeneic skin to perimetamorphic controls, routinely induces tolerance towards implant-strain skin grafts applied in adult life. To characterize this allotolerance further, additional in vivo approaches were attempted. Injection of gamma-irradiated (5000 rads) implant-strain splenocytes into frogs bearing tolerant skin grafts revealed (within 3 days) significantly elevated tritiated thymidine uptake by host spleen cells, compared to siblings injected with isogeneic cells. Although this in vivo 'mixed leucocyte reaction' proved to be thymus dependent, the identity of the cells involved awaits clarification. When non-restored Tx Xenopus are injected with live MHC-disparate splenocytes, graft-versus-host (GVH)-induced mortality ensued within 2 weeks. Such GVH disease also occurred (albeit more chronically) when Tx allothymus-implanted animals were given MHC-incompatible splenocytes, but only when these came from the thymus donor strain. Splenocytes from thymus-implanted animals failed to achieve GVH-induced splenomegaly when transferred to appropriate hosts (bearing MHC antigens of the thymus donor strain). Overall, the experiments indicate that alloreactivity against donor cells is impaired but not completely inhibited in Xenopus following perimetamorphic implantation.
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PMID:In vivo studies on allotolerance perimetamorphically induced in control and thymectomized Xenopus. 296 Jun 13

Using the genetic model of Prague recombinant congenic lines of chickens we found that incompatibility in the B-G region of the major histocompatibility complex (MHC) causes very severe graft-versus-host reaction (GVHR)-associated haemolytic anaemia in newly hatched chickens. Unexpectedly, mild or no signs of this GVH disease are elicited when a recipient chick and an adult donor of lymphocytes are incompatible in the whole B haplotype (B-F/L + B-G regions). On the other hand, the B-G region incompatibility alone (as has been described previously) is not sufficient to produce any GVH splenomegaly in embryos at 14 days of incubation. However, GVH splenomegaly in the donor-recipient combinations with the difference in the whole B haplotype (B-F/L + B-G regions) is significantly greater than in those with the B-F/L region difference only. These results confirm that the B-G region genes of chicken MHC are also involved in the histocompatibility reactions. Furthermore, a new hypothetical model for the structure of the chicken MHC is discussed.
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PMID:The B-G region genes of the chicken MHC are responsible for lethal graft-versus-host disease in newly hatched chickens. 339 29

Transfer of parental strain T lymphocytes into F1 hybrid rats differing with respect to gene products of the major histocompatibility complex (MHC) causes a graft-versus-host (GvH) reaction. This reaction results from recognition of host allogeneic MHC gene products by specific clones of donor T cells. When given systemically in sufficient numbers, these donor T cells cause a progressive, generally fatal wasting syndrome, an early feature of which includes extensive splenomegaly. A more local, non-fatal GvH reaction, marked by extensive enlargement of the draining lymph nodes, ensues when donor T cells are administered via the footpad. Here, we demonstrate that cells derived from the enlarged draining lymph nodes of A/B F1 animals undergoing local GvH disease caused by donor A T cells contain a subpopulation of host-derived killer T-cell precursors which can be activated to lyse specific blast cells, derived from mixed lymphocyte culture (MLC), reactive to host MHCb alloantigens. These 'anti-idiotypic' cytolytic T cells lyse A anti-MHCb MLC blasts, and also, they lyse anti-MHCb MLC blasts from MHC different, third party rat strains.
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PMID:Anti-idiotypic cytotoxic T cells in rats with graft-versus-host disease. 660 95

In order to determine whether a given H-2 haplotype has similar effects on responses to schistosomiasis mansoni on different genetic backgrounds, mice of 2 pairs of congenic strains (H-2b and H-2k on BALB/c and C57BL/10 backgrounds) were infected. Worm burdens, mortality, splenomegaly, tissue and faecal egg counts, and antibody titres to worm and egg antigens were measured. The genetic background had a major effect on the genesis of splenomegaly, on the deposition of eggs in the spleen, the maximum faecal egg count, the antibody titre to egg and worm antigens and the rate of generation of antibody response. The H-2 haplotype was shown to consistently influence the maximum faecal egg count and the antibody titres. Worm burden was not influenced by genetic differences between strains and mortality differences were not significant. The data presented here indicate that the effect of the major histocompatibility complex on responses to infection is greatly influenced by the genetic background on which it is expressed.
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PMID:The influence of the H-2 complex on responses to infection by Schistosoma mansoni in mice. 683 96

AKR mice were protected from lethal irradiation and established as long-lived chimeras by transplanting allogeneic C57BL/6 (B6) bone marrow that had been treated in vitro with anti-Thy-1 antiserum without complement. In these chimeras, which were designated [B6 {arrow} AKR], virtually all the thymus and spleen cells were shown to be derived from the B6 donor; several immune functions studied in these chimeras were as follows: (a) The chimeric mice were tolerant of histocompatibility antigens of both donor and recipient strain and nearly fully reactive to antigens of third party, as revealed by Simonsen's splenomegaly assay. The tolerance of these chimeras could not be attributed to suppressor cells but was compatible with clonal depletion. (b) Proliferative responses to concanavalin A, phytohemagglutinin, and lipopolysaccharide as well as natural killer and antibody-dependent cell- mediated cytotoxicity activity of the chimeric mice was normal. (c) Plaque- forming cell (PFC) assays of antibody responses to sheep erythrocytes (SRBC) showed gross deficiency in the primary response of the [B6 {arrow} AKR] and [AKR {arrow} B6] chimeras. By contrast, [B6-H-2(k)(E(k)) {arrow} AKR] H-2-compatible chimeras and [AKR {arrow} AKR] syngeneic marrow transplanted mice had normal primary PFC responses. PFC responses after secondary stimulation with SRBC, however, revealed vigorous direct plaque formation and substantial but somewhat smaller indirect plaque formation in the [B6 {arrow} AKR] chimeras. This observation favors operationally the concept of adaptive differentiation proposed by Katz et al. (44). (d) Analysis of ability of the chimeras to develop and express delayed-type hypersensitivity responses to contact sensitizer (2,4-dinitro-l-fluorobenzene [DNFB]) showed no apparent immunodeficiency of either chimeras to this form of immunization. Development of immunologic tolerance to DNFB, however, was grossly deficient in [B6 {arrow} AKR] chimeras but normal in [AKR {arrow} AKR], [B6 {arrow} B6], and [E(k) {arrow} AKR] chimeras. These findings indicate that full chimeras across major histocompatibility complex have considerable immunologic vigor even though primary immune responses that require histocompatibility between interacting cell types are initially defective.
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PMID:Humoral and cell-mediated immune responses in fully allogeneic bone marrow chimera in mice. 698 46


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