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)

We explored the immunoincompetence of mice undergoing a chronic graft-vs-host reaction (GVHR) across minor histocompatibility barriers. BALB/c and B10.D2 mice are H-2d and mls b, and differ only with regard to minor histocompatibility antigens (MiHA). A large number of BALB/c mice were unirradiated or were irradiated with 300, 600, or 900 R. They then were injected with 5 X 10(7) spleen cells from either allogeneic B10.D2 or syngeneic BALB/c mice. The spleen cells from these recipient mice were assayed at various times post-irradiation/injection for their proliferative response to Con A and LPS, their ability to suppress the mitogen responses of normal spleen cells, and for the genetic specificity of this suppression. Spleen cells from BALB/c mice that had received 600 or 900 R (but not 0 or 300 R), and allogeneic B10.D2 lymphocytes, became very hyporesponsive to mitogens and became suppressive in vitro by days 7 to 10 post-irradiation/injection. These phenomena persisted for the entire 49 days of the experiment. After an initial period of splenomegaly, the spleens of these mice gradually became depleted of viable lymphocytes. Initial characterization of suppressor cells found in the spleens of GVH mice showed that they were not removed by treatment with anti-Thy-1.2 plus complement. GVH suppressors also were not adherent to plates coated with antiserum directed towards murine Ig. In addition, these cells did not adhere to plastic plates. Thus, we believe that the suppressor cells found in mice undergoing GVHD across MiHA are not mature T cells, B cells, or macrophages, but belong to a class of suppressor cells termed natural suppressor (NS). Genetic analysis of NS cell activity showed that as early as 10 days post-irradiation/injection, NS cells inhibited mitogen responses of all mouse strains tested, the exception being the relative difficulty in suppressing the LPS response of B10.D2 (syngeneic with donor cells). By day 42, this had developed into an almost complete inability to suppress a B10.D2 LPS response, although at this time NS cells were still capable of inhibiting all the other mitogen responses of all strains tested, including the Con A response of B10.D2 spleen cells. Moderate amounts of mitogen unresponsiveness and suppressor activity were seen in the syngeneic groups (BALB/c----BALB/c) but only if recipients received 600 or 900 R. This was a transient phenomenon that was maximal at day 14, and which we believe to be a similar but less severe degree of immunoincompetence when compared with that seen with allogeneic stimulation in the B10.D2----BALB/c GVH model.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Graft-vs-host reactions (GVHR) across minor murine histocompatibility barriers. II. Development of natural suppressor cell activity. 316 Jul 74

We have been studying the mitogen hyporesponsiveness and immunosuppression induced in chronic murine graft-vs.-host disease (GVHD) induced across minor histocompatibility (MiHA) barriers. In this system, donor and recipient mice are major histocompatibility complex- and mls-identical, and are nonreactive in primary mixed leukocyte reactions. Spleen cells from B10.D2 (H-2d, mls b) mice were injected into irradiated (600 rad) BALB/c (H-2d, mls b) recipients. Recipient spleen cells are hyporesponsive to mitogens, and contain natural suppressor (NS) cells. We investigated the cellular requirements for both the in vivo induction and the in vitro expression of this GVH suppression. T cells are required in the graft, but they are not sufficient to induce suppression, and a non-T cell population is also required for maximum induction in vivo. T cells are also required for the maximum expression of NS cell suppressive ability in vitro. Early in the course of GVH, the suppressor cells are able to suppress the Con A and LPS response of all mouse strains tested (except for the relative difficulty in suppressing the B10.D2 LPS response). Later, they become almost completely unable to suppress the B10.D2 LPS response; while still being able to suppress the Con A and LPS response of all other strains tested (including the B10.D2 Con A response). This inability to suppress a B10.D2 LPS response can be brought back to almost complete suppression by the addition of concanavalin A supernatant (CAS). We present a hypothesis to explain what may be a common mechanism for GVH-induced suppression, total lymphoid irradiation-induced suppression, and neonatal tolerance. These situations all include rapidly proliferating lymphohematopoietic stem cell populations, and also have large numbers of NS cells. NS cells can suppress proliferating lymphoid populations, and their development and activity are greatly enhanced by T cell signals such as are supplied by donor T cells in chronic GVHD. Thus, NS cells may feed back on and downregulate self-reactive T cells or T cells responding to introduced foreign antigens.
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PMID:Synergism between T and non-T cells in the in vivo induction and in vitro expression of graft-vs.-host disease-induced natural suppressor cells. 316 77

We examined whether nude mice, which are deficient in T cell function, could be used as a model for induction of lethal graft-versus-host disease. Nude mice injected with MHC-disparate spleen cells exhibited only transient GVH reaction such as splenomegaly. Inoculation of B6 spleen cells into BALB/c nude mice produced high titers of alloantibodies to the donor cells. These alloantibodies eliminated host-MHC-reactive donor T cells from the host. After abolition by 400 rads irradiation of the capacity of nude mice to produce antibody, lethal GVHD could be induced by allogeneic spleen cell transfer and was mediated by donor T cells. This lethal GVHD was prevented by prior administration of antidonor alloantibody to the irradiated recipients at least 24 hr before donor-cell grafting. The role of alloantibody was substantiated in 2 other combinations in which little or no alloantibodies to donor spleen cells were produced. Engraftment of either MHC-identical but non-MHC disparate donor spleen cells into BALB/c nude mice or of parental spleen cells into F1 nude mice resulted in death mediated by T cells. In addition, irradiated BALB/c nude mice inoculated with non-MHC-incompatible B10.D2 spleen cells were much more sensitive to alloaggression by the donor cells than were nonirradiated hosts, indicating the presence of some radiation-sensitive component(s) acting in nude mice against GVHD induction by donor T cells. Thus the nude mouse is considered to be a useful recipient for clarifying the basic mechanisms involved in lethal GVHD.
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PMID:Lethal graft-versus-host disease in nude mice. I. Establishment of model systems. 326 65

Highly purified populations of C57BL/6 (B6) L3T4+ and Lyt-2+ T cell subsets were compared for their capacity to exert alloreactivity to class I vs. class II H-2 differences in vivo. B6 Lyt-2+ cells responded strongly to the class I different mutant, bm1, as manifested by DNA synthesis in the spleen of irradiated mice followed by entry of blast cells into thoracic duct lymph, induction of splenomegaly in newborn mice, production of lethal GVHD in irradiated mice, and skin allograft rejection. By all of these parameters, B6 Lyt-2+ cells showed almost total unresponsiveness to the class II-different mutant, bm12. Reciprocal results were observed with B6 L3T4+ cells, these cells responding strongly against bm12 but not against bm1. In the case of purified T cell subsets from other strains, CBA/Ca and B10.BR L3T4+ cells both responded well to a full H-2 difference. Responses by Lyt-2+ cells from these strains were weaker, especially for CBA/Ca cells. The implications of these findings are discussed.
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PMID:Properties of purified T cell subsets. II. In vivo responses to class I vs. class II H-2 differences. 351 63

We studied the morphologic and immunophenotypic characteristics of inflammatory infiltrates in the skin of mice with acute graft-versus-host disease induced by bone marrow transplantation between strains differing only in minor histocompatibility antigens. The strain combinations employed (B10.Br - greater than CBA) have been shown to produce a lethal graft-versus-host disease with clinical severity proportional to the number of T lymphocytes added to the donor marrow inoculum. Transplant recipients developed pronounced clinical signs of graft-versus-host disease, including copious diarrhea and weight loss, and histologic alterations in skin strikingly similar to this disease in humans. Our findings indicate that the preponderant mononuclear cell in lesional skin from these animals has phenotypic characteristics of a natural killer cell. This cell was often found in apposition with necrotic epidermal cells. The origin, function, and potential relevance of natural killer cells in lesion formation in this experimental model are discussed.
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PMID:Acute cutaneous graft-versus-host disease to minor histocompatibility antigens in a murine model. Evidence that large granular lymphocytes are effector cells in the immune response. 352 39

Graft-versus-host disease (GVHD) can occur in bone marrow-transplant recipients even when donor and host are identically matched at the major histocompatibility complex. GVHD in this context presumably arises because of differences in minor histocompatibility antigens. Murine GVHD to minor histocompatibility antigens has been studied in an effort to determine whether skin is a target of the immune response in this model system. T cell-depleted marrow cells (10(7)) from B10.BR (H-2k) mice were supplemented with varying numbers of nylon wool-enriched splenic B10.BR T cells and transplanted intravenously into irradiated (1100 R) CBA (H-2k) mice. Sequential biopsies of ear skin were obtained at weekly intervals over a 7-week period. Histopathologic evaluation revealed basal cell layer vacuolization, exocytosis, and satellitosis of mononuclear cells in the epidermis. Dyskeratosis was observed only in animals receiving T cells, and proved to be the most reliable histologic parameter of disease with the number of dyskeratotic cells per linear millimeter of epidermis correlating both with severity of clinical disease and with the number of transplanted T cells. Ultrastructural examination revealed exocytosis of mononuclear cells into the epidermis where they were frequently apposed to degenerating and necrotic keratinocytes. These data indicate that the skin is an informative target organ for study of experimental GVHD to minor histocompatibility antigens.
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PMID:Cutaneous acute graft-versus-host disease to minor histocompatibility antigens in a murine model: histologic analysis and correlation to clinical disease. 352 9

Highly purified human recombinant interleukin 2 (IL-2) markedly accelerated lethal GVHD in the H-2-identical B10.BR----CBA combination, but had no effect when the donor cells were depleted of mature (Thy-1.2-positive) T lymphocytes, indicating a strong immunopotentiating effect of IL-2 on mature T cells causing GVHD. In the same donor-host combination, IL-2 did not influence the recovery from the post-transplantation bone marrow aplasia. The results suggest that IL-2 could be considered for adjuvant hormonal therapy to enhance immune recovery in recipients of T-cell-depleted allogeneic marrow.
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PMID:T-cell depletion of allogeneic bone marrow prevents acceleration of graft-versus-host disease induced by exogenous interleukin 2. 354 38

A minor (non-H-2) graft-vs.-host reaction (GVHR) was induced in adult irradiated (DBA/2 X B10.D2)F1 mice by hematopoietic parental B10.D2 cell grafts. Syngeneic (F1) cell transplantation was performed as control. In one set of experiments T4 plasma level (enzyme linked immunosorbent assay) was systematically followed up in individual GVHR and control mice. Compared to the control, GVHR triggered off a significant and sustained decrease of T4 plasma level. In another set of experiments, TSH plasma levels (RIA) were measured in killed animals. GVHR induced an early elevation of plasma TSH. In a third set of experiments, mice undergoing GVHR received daily injections of L-T4 (0.03, 0.15, or 0.3 microgram/mouse). Compared to the control (saline injected) GVHR mice, T4 supply did not improve GVHR state. No positive effect of the high dose and rather a negative effect of both lower doses especially on glucose plasma concentration, were observed. All these data suggest that thyroid gland is primarily and very early involved in the onset of the GVH disease.
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PMID:Endocrine involvement in minor (non-H-2) graft-versus-host reaction in mice. Early and primary thyroid failure. 356 37

A chronic GVH reaction (detected by T cell immune deficiency) was induced in unirradiated, adult (C57BL/10 X B10.A)F1 mice by injecting them i.v. with 3 X 10(7) B10.A parental spleen cells. Thirty-four days later, attempts were made to reconstitute the GVH immune-deficient mice by whole-body irradiation and repopulation with bone marrow cells from normal syngeneic F1 mice. The reconstituted mice were tested for CTL responses 147 and 272 days after repopulation with normal F1 bone marrow. These GVH/chimera mice remained immunoincompetent for at least 272 days for CTL responses to hapten-self and H-2 allogeneic antigens.
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PMID:Failure of bone marrow cells to reconstitute T cell immunity in graft-vs-host mice. 388 28

In our model of GVHR, irradiated (DBA/2 X B10.D2)F1 mice were given splenic and bone marrow cells from B10.D2 donor mice. At different set times after the graft, recipient mice were given a single injection of a radioactive precursor of DNA (125IUdR) and killed one hour later. The radioactivity in excised organs reflected the label incorporation by the proliferating cells. When mice were killed from 1 hour to 96 hours after the label injection the residual radioactivity in individual organs reflected the number of the residual living cells arising from cells which were in S-phase during the label pulse. This study allowed us to specify the dynamics of the cell proliferative activity and the behavior of these proliferating cells through the whole organism at any time of a GVH disease. A very interesting point is that the minor non-H-2 histocompatibility antigens (MiHA) responsible of the GVHR induced a very important and specific stimulation of the grafted cell proliferation in all the non-lymphoid organs with a spatial and timing evolution through the whole organism. A great part of the cells specifically stimulated to divide by the MiHA are very short-lived. The remaining living cells migrate out of the spleen and bone marrow and accumulate into the non-lymphoid organs after a latency period lasting 12-24 hours following the label uptake. This cell invasion was mainly into the liver, vesicular glands, kidneys, salivary glands and lungs.
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PMID:Proliferation and migration of grafted hemopoietic cells during a graft-versus-host reaction induced by minor non-H-2 histocompatibility antigens in the mouse. 391 Jan 29


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