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

Mouse yolk sac cells on day 9 of gestation were found to elicit a GVH response, measured by enlargement of the local popliteal lymph nodes. The response cannot be attributed to contaminating maternal cells, since F1 (Balb/c x C57B1) yolk sac cells did not cause a reaction in F1 (Balb/c x C57B1) hosts. On the other hand, yolk sac cells did not elicit a detectable MLC reaction, nor did they respond to PHA or Con A. Hence, mouse yolk sac cells have the potential to express a certain limited array of immunological reactivities, before the development of embryonic thymus and liver.
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PMID:Immunological potential of yolk sac cells. 13 74

Bone marrow transplantation using an HLA-MLC-identical sibling is the most valuable treatment of severe aplastic anemia.2,6,7 Between November 1973 and March 1977, 25 consecutive patients have been treated by marrow transplantation in our unit. Nine patients are alive with complete hematologic restoration between 3 months and 3 years. The high mortality can be largely accounted for by marrow graft rejection (14 patients). Despite the small number of patients, we have tried to identify prognostic factors associated with marrow graft rejection. They are mainly the existence of anti-HLA antibodies, the sex difference, and the normal PHA and MLC response before grafting. After the graft, the disappearance of anti-HLA antibodies has a good prognostic value. The appearance of autolymphocytotoxins seems to correlate strongly either with rejection or graft-versus-host disease.
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PMID:Allogeneic bone marrow transplantation in aplastic anemia--report of 25 cases. 34 52

We studied the effect of depleting NK1.1+ cells from an allograft of lymph node and spleen cells on the outcome of GVH disease in the parent----F1-hybrid combination C57BL/6----(C57BL/6xDBA/2)F1. Four treatment groups were established: group I mice were transplanted with an unmodified graft from normal donors; group II mice were transplanted with an NK1.1-depleted graft that had been harvested from normal donors; group III mice received grafts from donors that had been injected with Poly I:C (100 micrograms i.p.) 18 hr prior to harvesting (These grafts were incubated with complement, but no antibody.); group IV mice were transplanted with depleted grafts harvested from donors that had received Poly I:C. Recipients in each group were monitored for splenomegaly, mitogen responsiveness, NK and CTL activity, histopathology, weight loss, and mortality. Results showed that recipients in all four groups developed splenomegaly and unresponsiveness to LPS, PHA, and Con A by day 12. Augmented host-derived NK activity and graft-derived antihost CTL activity was also demonstrated. Group IV showed little or no weight loss, minimal histopathological changes and a marked reduction in mortality. Recipients in all other groups developed features characteristic of GVH disease and exhibited a steady decline in body weight beginning by day 12. Mortality generally began on day 18 and reached 75-90% by day 60. We postulate that anti-NK1.1 depletes cells from the graft are intimately connected with the effector mechanism in acute GVH disease.
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PMID:Prevention of acute lethal graft-versus-host disease in F1 hybrid mice by pretreatment of the graft with anti-NK-1.1 and complement. 163 23

Twenty-nine patients with advanced leukemias (median age 34 years) received histocompatible sibling marrow that had been depleted of T cells by ex vivo incubation with anti-CD5 monoclonal antibody-ricin immunotoxin (T101-R) for the purpose of graft-versus-host disease prophylaxis. Donor cell engraftment was documented in 28/29 patients by DNA restriction fragment length polymorphisms. In this pilot study the dose of T101-R incubated with donor marrow was increased in a stepwise manner from 300 ng (10 patients) to 600 ng (5 patients) to 1000 ng immunotoxin (IT)/10(7) bone marrow mononuclear cells (14 patients) in an attempt to achieve more effective GvHD prophylaxis. A statistically significant reduction in acute GvHD was achieved for patients receiving marrow pretreated with 1000 ng of immunotoxin (34%) compared to recipients of BM treated with 300 ng immunotoxin (100%, P = 0.0004). T-depleted marrow samples were evaluated for residual T cell activity using several in vitro assays including proliferation to the purified mitogen PHA (HA-17) and in mixed lymphocyte culture (MLC), T cell cytotoxicity, a limiting dilution assay for detecting precursors of proliferating T cells (LDApPTL), and phenotypic analysis of viable T cells expanded in 16-day culture with interleukin 2. The extent of T cell depletion determined by LDA assay varied widely at each immunotoxin concentration used. Thus, there was no correlation between the dose of T cells infused and subsequent GvHD. Phenotyping of lymphocytes recovered from immunotoxin-treated marrow demonstrated that residual T cells were CD5 negative in all cases tested. The only in vitro parameter that predicted subsequent acute or chronic GvHD was the demonstration of viable CD5 negative lymphocytes with T cell phenotype (CD2, CD3, and/or CD7 positive) after 16-day culture with IL-2 of the T-depleted bone marrow. We observed that such CD5 negative cells expressing other T cell markers have cytotoxic function and speculate that these cells may be capable of mediating GvHD in allogeneic transplantation.
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PMID:T cell depletion with anti-CD5 immunotoxin in histocompatible bone marrow transplantation. The correlation between residual CD5 negative T cells and subsequent graft-versus-host disease. 169 19

Cytotoxic T lymphocyte precursor (CTLp) frequency assays were examined in patients with chronic myeloid leukaemia (CML) following bone marrow transplantation (BMT) using recipient lymphocytes or CML cells as targets in a 51Cr release cytotoxicity assay. Eighteen patients were studied; 11 received marrow from a fully HLA A, B and DR matched sibling donor, and six from matched unrelated donors or a partially matched sibling (one patient). Two of the unrelated donor transplant recipients received marrow depleted of T lymphocytes, and the remainder received unmanipulated marrow and cyclosporin with or without methotrexate as prophylaxis against graft-versus-host disease (GVHD). Donor cells tested before BMT did not generate CTL against the patients' leukaemia, but up to 9 months after BMT a low frequency of CTLp directed against the patients' CML cells (Lk-CTLp) was detected in all patients. The Lk-CTLp frequency was significantly lower than the frequency of CTLp directed against the recipients' PHA transformed pretransplant lymphocytes (Ly-CTLp) (p less than 0.05). Lk-CTLp showed MHC restricted cytotoxicity and did not demonstrate cytotoxicity in an NK assay. The Lk-CTLp frequency correlated with both GVHD severity and relapse: severe GVHD was only seen with Lk-CTLp frequencies greater than 1:400,000, while leukaemic relapse was only observed in two patients with Lk-CTLp frequencies less than 1:400,000. These results show that a low frequency of alloreactive cells of presumed donor origin with cytotoxic potential against residual leukaemia normally circulate after BMT. Their relationship with the graft-versus-leukaemia phenomenon and their cross-reaction with GVHD reacting cells remain to be determined.
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PMID:Graft-versus-leukaemia following allogeneic bone marrow transplantation: emergence of cytotoxic T lymphocytes reacting to host leukaemia cells. 175 22

Patients who undergo allogeneic bone marrow transplantation (BMT) are clinically immunodeficient for a prolonged period after engraftment. In the present study, we examined immune function after BMT in a series of patients who had received HLA compatible sibling marrow grafts purged of T cells with anti-CD6 monoclonal antibody and complement. None of the patients in this analysis received immunomodulating agents and none had developed graft-versus-host disease (GVHD). Initially after BMT, natural killer (NK) cells are the predominant cell type, giving way to CD3+, CD5+ T cells after 4 to 8 weeks. Despite the return of normal numbers of T lymphocytes post-BMT phenotypic analysis reveals several long-term abnormalities, including an inverted T4:T8 ratio and a significant fraction of CD3+ T cells that do not co-express CD6. In mitogenic assays, stimulation by either nonspecific lectin (phytohemagglutinin; PHA) or antibodies to the CD2 surface structure (anti-T11(2) + anti-T11(3)) results in decreased levels of T-cell proliferation compared with controls for over 18 months post-BMT. In contrast, the ability of unstimulated peripheral blood mononuclear cells (PBMC) to respond to recombinant interleukin-2 (rIL-2) is relatively intact, most likely reflecting early functional reconstitution of the NK cell population. To further characterize the prolonged abnormalities in T-cell proliferation after PHA or CD2 stimulation, we examined more proximal events in T-cell activation such as induction of IL-2 receptor expression and stimulus-induced intracellular calcium flux. We found that the induction of IL-2 receptor (p55) after in vitro activation, although initially abnormal, recovers completely by 6 months post-BMT. We also found that, after CD2 stimulation, calcium flux in T cells was normal immediately after engraftment. In contrast, after stimulation with anti-CD3 antibodies, a large population of T cells do not develop intracellular calcium flux compared with controls. We conclude that despite the recovery of normal numbers of T lymphocytes early after engraftment of CD6-depleted marrow, these T cells exhibit several physiologic and functional abnormalities that persist for varying intervals post-BMT. At present, it is unclear which of these specific defects is most closely associated with increased susceptibility to infectious agents after BMT.
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PMID:Reconstitution of T-cell function after CD6-depleted allogeneic bone marrow transplantation. 197 Sep 38

We studied T cell blastogenesis in stored blood during the preservation time within 7 days. Blood samples were obtained from 8 adults and stored at 4 degrees C immediately after donation with CPD (citrate-phosphate-dextrose) for 3,5 and 7 days. After each intervals, mitogenic responses of T cells from the samples in the presence of an optimal dose of PHA as a mitogen and MLR (mixed lymphocyte reaction) with lymphocytes prepared by 2000 rad radiation from other 10 donors as stimulating cells were investigated. The stimulation index (S.I.) of PHA as a responsibility of the stored blood was decreasing to 86.7 +/- 24.8%, 44.2 +/- 12.5% and 31.2 +/- 11.1% in proportion of that of fresh blood after 3, 5 and 7 days preservation. The S.I. of MLR were in the same way decreasing to 92.5 +/- 21.8%, 45.9 +/- 9.8% and 33.3 +/- 10.1% after that. These observations suggest that lymphocytes in stored blood within 7 days are able to induce GVHD (graft-versus-host disease) in open heart surgery of which immunological activity is thought to be decreased by extra-corporeal circulation. We concluded that the stored blood within 7 days should be irradiated to 1500 rad or more in order to prevent GVHD.
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PMID:[T cell blastogenesis in stored blood can induce GVHD in open heart surgery]. 214 65

Spleen cells from mice receiving TLI, with or without thymus shielding, were investigated for in vitro and in vivo defects. At 4-6 weeks after irradiation spleen cells of both groups showed a normal number of Thy1 (T cells), L3T4 (CD4 positive T cells) cells, and an absence of natural suppressor cells. Splenocytes of the nonthymic shielded TLI group were not able to mount either a normal in vitro response (in MLR or PHA) or an in vivo graft-versus-host-disease reaction when injected into lethally irradiated adult allogeneic recipients or into neonatal F1 hybrids. This was in contrast to the normal immune capacity of spleen cells from the thymus shielded group that gave normal MLR and PHA tests in vitro and provoked GVHD in vivo. Thymuses recovered from mice receiving TLI with or without thymic shielding were however equally efficient in restoring the immune capacity after transplantation into neonatally thymectomized mice as measured by the PHA assay. Thymic irradiation is therefore necessary but not sufficient for creating long-lasting immune defects after TLI.
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PMID:Effects of thymus irradiation on the immune competence of T cells after total-lymphoid irradiation. 236 57

Peripheral blood mononuclear cells (PBMC) from 21 patients after bone marrow transplantation (BMT) were studied for their capacity to produce interferon (IFN) in vitro. The basal and IFN-stimulated 2-5 A synthetase activity was also investigated as a marker of the cells' ability to respond to exogenous IFN. All but one patients received cyclosporin A as a prophylaxis against graft-versus-host disease (GVHD). GVHD was diagnosed in three patients. IFN production in response to stimulation with phytohemagglutinin or poly I:C was not detectable in most patients without GVHD until 7 months after grafting. However, in a proportion of recipients without GVHD, studied early after BMT, transient normal IFN production was observed. In contrast to patients without GVHD, PBMC from patients with GVHD produced stable high levels of IFN when stimulated in vitro. The impairment of IFN production did not correlate with conditioning regimens, infection, plasma cyclosporin levels or the lymphocytes' blastogenic response to the mitogens. Addition of interleukin-2 (IL-2) to culture medium of fresh unresponsive PBMC restored only partially the defective IFN production. Similarly, T-cell lines propagated in IL-2 conditioned medium, from unresponsive PBMC, produced low levels of IFN gamma when stimulated with PHA. The basal activity of 2-5 A synthetase in PBMC from patients without GVHD could not be stimulated, during the first 3 months after BMT, by the cultivation of cells with IFN alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kinetics of restoration of interferon production after bone marrow transplantation in man. 245 87


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