Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Germfree allogeneic bone marrow chimeras (ABMC) were produced by the i.v. injection of approximately 10(7) bone marrow cells from germfree DBA/2 mice into lethally irradiated germfree C3H mice. In the germfree state, the short-term ABMC showed no histologic signs of graft-vs-host reactions (GVHR), yet splenic lymphocytes were unable to respond to PHA, Con A, or SRBC. Attempts to remove responsiveness by the implantation of a DBA/2 thymus under the host kidney capsule also resulted in failure. However, when the donor thymus was enclosed in a cell-impermeable chamber to eliminate a GVH reaction, responsiveness to Con A was restored. The PHA and SRBC responses were unaffected by this treatment. Daily injections of thymosin caused both an increased Con A response and increased numbers of PFC, although the PHA response was again unaffected. Thus, soluble substances from thymic tissue can be used to overcome partially the histocompatibility barrier present in the ABMC that affects at least two different functional cell populations.
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PMID:Studies on the mitogen responses of germfree allogeneic chimeras. II. Maturation of two cell types and partial restoration of responsiveness of the short-term chimeras. 2 5

Mice homozygous for the recessive mutation motheaten (me) are deficient in capacity for immune response but show an elevated level of serum immunoglobulins. In comparison to spleen cells from normal sibs, spleen cells from me/me mice have a severely depressed 19S PFC response to SRBC. In the GVH assay, spleen and thymus cells from motheaten donors caused significantly weaker reactions than like cells from normal sibs. Serum electrophoretic patterns of motheaten mice showed increased levels of alpha-, beta-, and gamma-globulins and decreased levels of albumin. Increases in quantities of all major classes of immunoglobulins were found in serum of me/me mice 5 weeks of age and older. Elevation of serum IgM was evident by 3 weeks of age and had reached 25 times the levels in normal sibs by 6 weeks of age. Immunoelectrophoresis and Ouchterlony analysis showed motheaten serum to have both kappa and lambda2 light chains. Evidence of autoimmunity was found in motheaten mice in the granular deposition of IgM and IgG in kidney glomeruli. Motheaten mice, thus, appear to have a severe immune deficiency, but the basic nature of the deficiency is not yet known.
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PMID:Motheaten, an immunodeficient mutant of the mouse. II. Depressed immune competence and elevated serum immunoglobulins. 5 6

Cells from the spleens of mice were separated into seven subpopulations by centrifugation on a discontinuous density gradient of dextran. The lightest fraction (containing stem cells), the three heaviest fractions (containing small lymphocytes), or a mixture of these, were injected into thymectomized or sham-thymectomized irradiated mice together with sheep red blood cells as antigen. After 8 days, the spleens of treated mice were tested for their content of cells lysing sheep red blood cells in agar (PFC) or cells mounting graft-versus-host reaction in newborn mice (GVHR). Heavy fractions were depleted of progenitors of PFC, but contained progenitors of cells mounting GVHR. The light fraction was depleted of both. If light cells were given together with heavy ones, the potential to generate PFC was restored, but only if the recipients were without their thymus; by contrast, the potential to generate GVH-reactive cells was strongly suppressed in the absence of a thymus. It is concluded that, in this model, stem cells probably interact with immunocompetent cells, and that the interaction depends on the thymus.
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PMID:Thymic influence of proliferation and interaction of fractionated spleen cells of mice. 126 54

We have been investigating the effects of polyinosinic:polycytidylic acid (pI:C), an interferon inducer, on the graft-versus-host reaction. We have previously shown that pI:C treatment of C57BL/6xAF1 (B6AF1) recipient mice immediately before injection of C57BL/6 (B6) parental lymphocytes inhibited the immuno-suppression and pathological changes normally caused by the GVH reaction, by a mechanism apparently identical to that seen in F1 hybrid resistance (HR) to hematopoietic grafts. We now demonstrate that delaying pI:C treatment by as little as 48 hr produces the opposite effect. Treatment of recipient B6AF1 mice at different days after transfer of parental lymphocytes induced a marked increase in the severity of the GVH reaction, as measured by a decreased plaque-forming cell response to sheep erythrocytes; decreased proliferative response to the T and B cell mitogens PHA, Con A, and LPS; increased pathological changes in both lymphoid and nonlymphoid tissues; and increased GVH-associated mortality. This effect is unrelated to HR, as pI:C was able to augment the severity of the GVH reaction when A strain cells were injected into AxCBAF1 recipients, which do not manifest HR. Early pI:C treatment (1 and 2 days after parental cell transfer) increased the severity of the GVH reaction much more than later pI:C treatment (7 and 8 days after parental cell transfer). This observation, along with the demonstration of altered pathology in GVH mice treated with pI:C, suggests that the effect of pI:C is not mediated through a direct suppressive effect of IF on the cells responding in either the PFC or mitogen assays, but rather by the ability of IF to activate or suppress mechanisms involved in the development of GVH-induced alterations.
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PMID:The effects of polyinosinic:polycytidylic acid on the graft-versus-host reaction. III: Increased severity of the reaction with delayed pI:C treatment. 274 89

Spontaneous plaque-forming cells (S-PFC) were followed in 67 bone marrow transplantation (BMT) recipients and 41 controls. Patients with no acute graft-versus-host disease (GVHD) had decreased IgA and IgM S-PFC up to 7 weeks after BMT compared with controls. Patients with acute GVHD had increased IgG, IgA, and IgM PFC compared with controls and patients without GVHD during the first 4 weeks after BMT. The maximum number of S-PFC increased with increasing severity of acute GVHD. However, at diagnosis of GVHD there was no difference in S-PFC in patients who resolved their GVHD or in those who developed more severe GVHD. After 6 weeks, patients with acute GVHD had significantly decreased IgA and IgM S-PFC compared with normal. No major changes in S-PFC were induced during various infections. However, a patient who developed urticaria had a dramatic increase in S-PFC. Patients studied more than a year after BMT had reduced IgM S-PFC compared with controls. It is concluded that S-PFC are reduced after BMT, but markedly enhanced during acute GVHD.
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PMID:Polyclonal antibody secretion during acute graft-versus-host disease. 282 43

Graft-versus-host disease (GVHD), a serious complication of allogeneic bone marrow transplantation (BMT), can be prevented by in vitro depletion of T cells from the bone marrow (BM) prior to transplantation. The purpose of this study was to assess the role of BMT cells in the reconstitution of various immune functions following BMT across minor histocompatibility barriers. Lethally irradiated CBA/J (H-2k) mice were grafted with either 10(7) unseparated or T-cell-depleted BM cells from B10.BR (H-2k, minor-histoincompatible) mice. Blood counts, BM colonies in agar, and various immune functions of spleen cells from the recipient mice were tested 2-12 weeks post-BMT and compared with those of normal donors. The following observations were made: (A) Peripheral blood lymphocyte counts decreased to 30% of normal 2 weeks post-BMT with almost normal recovery at 8 weeks. (B) The percentage of Thy1.2+ splenocytes reached normal levels at 8 weeks post-BMT. (C) The number of BM colonies (GM-CFU) was reduced to 10% at 2 weeks and fully recovered at 12 weeks. (D) Proliferative response to the B-cell mitogen LPS was fully reconstituted after 4 weeks; however, anti-SRBC PFC (following Mishell-Dutton cultures) was restored 50% at 8-12 weeks. (E) Reconstitution of T cell functions including proliferative responses to concanavalin A, phytohemagglutinin, and allogeneic leukocytes, and allocytotoxicity, did not exceed 50% even 12 weeks post-BMT. Overall, depletion of T cells from donor BM allografts incompatible at minor histocompatibility loci, did not seem to significantly alter the rate of immunohematopoietic reconstitution in the lethally irradiated BM recipients.
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PMID:Bone marrow transplantation with T-cell-depleted grafts. II. Reconstitution of immunohemopoietic functions in lethally irradiated mice transplanted with unseparated or T-cell-depleted bone marrow grafts disparate at minor histocompatibility antigens. 295 82

A primary anti-NIP PFC response can be elicited by a GVH reaction provided certain structural requirements of the NIP-carrier are met. NIP-coated F(1) erythrocytes and NIP-coated parental erythrocytes give rise to substantial anti-NIP PFC responses in F(1) mice after the injection of parental spleens. These conjugates do not of themselves give rise to an anti-NIP PFC response and, in fact, normally give rise to NIP-specific tolerance. In contrast the GVH reaction is not able to enhance the primary anti-NIP PFC response to immunogenic NIP-conjugates.
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PMID:Induction of a primary antihapten response in vivo by a graft-vs.-host reaction. 414 78

IgE-levels are markedly elevated following bone-marrow transplantation in patients with and without GVHD. In patients with GVHD, there is a significant correlation between the timing of the IgE-increase and the appearance of clinical GVHD (p less than 0.01). The highest IgE-level (8000 kU/l) was noted in a recipient of a syngeneic graft. During the IgE-peak, the serum from this patient contained low concentrations of IgE reacting with several tested allergens as well as for the hapten TNP, which indicated polyclonal activation. In a patient with a known allergy to animal danders, RAST tests were positive against dog and cat both before and six weeks after total body irradiation and transplantation with marrow from a non-allergic donor. A slight increase in the amount of allergen-specific, IgE-antibodies was seen during the increase in total IgE. A non-allergic patient was transplanted with marrow from a donor allergic to timothy. Timothy-specific, IgE-antibodies were detected immediately after transplantation but they disappeared within a few days and could not be detected during the period of increase in total IgE. We believe that the IgE-elevation seen after conditioning with cytotoxic drugs and total body irradiation in BMT-patients is a polyclonal response in host B-cells induced during an acute, GVHR and influenced by disturbed regulatory T-cells. Lymphocytes from patients with acute GVHD had unusually large numbers of IgG/PFC in vitro after stimulation with staph. aureus Cowan 1 (p less than 0.001), which may reflect a clonal expansion of responsive B-cells.
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PMID:Are increased IgE-levels a signal of an acute graft-versus-host reaction? 634 26