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

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.
 ...
PMID:The B-G region genes of the chicken MHC are responsible for lethal graft-versus-host disease in newly hatched chickens. 339 29

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.
 ...
PMID:Properties of purified T cell subsets. II. In vivo responses to class I vs. class II H-2 differences. 351 63

Adult male (LewisXBrown Norway) F1 (LBNF1) rats received heterotopic small intestinal transplants from Lewis donors. Lewis-to-Lewis and LBNF1-to-LBNF1 isografts served as controls. All of the allograft recipients died after a median survival time of 16.2 days, but all isografted rats survived indefinitely. During the period of deterioration, allografted rats developed marked cutaneous erythema and became increasingly weak and cachectic. Histological changes of the skin, spleen, and grafts were characteristic of graft-versus-host disease (GVHD). There was a marked degree of relative splenomegaly. Injection of spleen cells obtained from LBNF1 rats with clinical GVHD into the foot-pad of syngeneic LBNF1 rats resulted in significant enlargement of the ipsilateral popliteal lymph node. The degree of lymph node enlargement was comparable to that induced in LBNF1 rats by injection of normal Lewis spleen cells. These results clearly demonstrate the ability of the small intestinal allograft to cause rapid and fatal GVHD in rats that are incapable of graft rejection.
 ...
PMID:Induction of graft-versus-host disease by small intestinal allotransplantation in rats. 387 31

Graft-versus-host disease (GVHD) was induced in (CBA X C57BL/6) F1 mice by i.v. injection of 50 X 10(6) parental spleen cells. The GVHD induced an enhanced NK (anti-YAC-1) cytotoxicity during the first 2 weeks after the spleen cell transfusion. This cytotoxic activity was shown to be mediated by asialo GM1-positive, partially Thy-1-positive and nylon-wool (NW) non-adherent cells, thus being classical NK cells. Depletion of NK-cell activity from donor and/or recipient mice with anti-asialo GM1 antibody prior to the spleen cell transfer did not prevent the GVHD as judged by the splenomegaly assay. Also, when NK activity was potentiated with polyinosinic-polycytidylic acid (pIC), no effect on the GVHD was seen. These data suggest that NK cells are not crucial for the development of GVHD in this model.
 ...
PMID:Natural killer (NK) cells and graft-versus-host disease (GVHD): no correlation between the NK cell levels and GVHD in the murine P----F1 model. 397 29

Immunologically mediated aplastic anemia (AA) was experimentally induced in mice by injecting 10(7) lymph node cells (LNC) from donor mice of one inbred strain to another H-2k identical but Mls mismatched strain previously given 600 rad total body gamma irradiation (TBI). AA developed after 2 weeks to 6 months in selected strain combinations used and usually 60 to 90% of the mice died. Clinical signs of graft-versus-host disease did not occur and splenic atrophy rather than splenomegaly was the rule. Histologically these mice had a lesion of the hematopoietic microenvironment characterized by sinusoidal injury and stromal necrosis. Others have demonstrated injury to hematopoietic stem cells. C3H/He LNC induced AA whereas C3H/HeJ LNC failed to induce AA. The C3H/HeJ strain carries a macrophage defect and these results suggest that a macrophage-like cell may be a mediator of immunological injury in this experimental model. Although all strain combinations evaluated were H-2k identical and Mls mismatched, certain Mls combinations resulted in AA and identical Mls mismatched but different strains did not. Both strong (Mlsd) and weak (Mlsc) stimulating LNC induce AA but simple Mls differences do not explain the AA as similar Mls combinations but different strain combinations fail to induce AA.
 ...
PMID:Experimental immunologically mediated aplastic anemia (AA) in H-2k identical, Mls (M) locus different mice. 661 89

Allogeneic bursal fragments or bursal cells (B 14 or B 19), grafted on the chorioallantois, induce splenomegaly in the recipient embryo (B 14 or B 19). This splenomegaly compares to that instigated by spleen cells. Syngeneic bursal grafts do not result in spleen enlargement. The reaction is thus caused by the MHC difference of the two lines used. We conclude that B cells may have a role in initiating the GVH-R.
 ...
PMID:[The bursa of Fabricius of chickens contains cells initiating the graft-versus-host reaction]. 681 56

Chronic and acute graft-versus-host disease (cGVHD and aGVHD) result from donor cells responding to host disparate MHC alleles. In cGVHD (H-2d-->H-2bd), heightened polyclonal immunoglobulin production is due to the interaction of donor allospecific helper T cells (Th) and the host B cells. In vivo administration of antibody to the ligand for CD40, gp39, blocked cGVHD-induced serum anti-DNA autoantibodies, IgE production, spontaneous immunoglobulin production in vitro, and associated splenomegaly. Antibody production remained inhibited for extended periods of time after termination of anti-gp39 administration. Antiallogeneic CTL responses induced in a GVHD were also prevented by the in vivo administration of anti-gp39 as was the associated splenomegaly. These data suggest that CD40-gp39 interactions are critical in GVHD and that CD40-gp39 may be a valuable ligand-receptor pair for targeting immunotherapeutic agents to control GVHD.
 ...
PMID:Antibody to the ligand of CD40, gp39, blocks the occurrence of the acute and chronic forms of graft-vs-host disease. 752 88

Two distinct T-cell glycoforms of CD43 result from differential glycosylation of a single gene product in vivo. The 115 kDa glycoform carries mainly tetrasaccharides and is a pan T-cell marker, whereas the 130 kDa glycoform carries mainly hexasaccharides and is associated with T-cell activation. CD43 has been shown to play a role both in enhancing and inhibiting cell adhesion; however, the function of the individual glycoforms is unknown. We have examined the distribution and regulation of the CD43 glycoforms in a murine model of acute graft-versus-host disease (GVHD) using monoclonal antibodies (mAbs) S7 and 1B11 specific for the 115 and 130 kDa CD43 glycoforms, respectively. An increase in T-lymphocyte CD43 130 kDa expression occurred during GVHD from day 4 onwards and coincided with splenomegaly and upregulation of the beta 1-6GlcNAc transferase (C2GnT), the key enzyme responsible for the addition of complex O-glycan branching to CD43. When T-lymphocyte subsets were examined for CD43 expression, we found that in GVHD, both CD43 glycoforms were upregulated on CD4+ T cells. However, in CD8+ T cells, CD43 115 kDa was downregulated while CD43 130 kDa was dramatically upregulated, such that two distinct CD8+1B11+ T-cell subsets were observed. These data demonstrate differential expression of the CD43 glycoforms in both resting and activated CD4+ and CD8+ T cells, and suggest that glycosylation differences between the CD43 glycoforms may reflect participation in the different functions of these T-cell subsets in immune disorders in vivo.
 ...
PMID:Differential regulation of CD43 glycoforms on CD4+ and CD8+ T lymphocytes in graft-versus-host disease. 753 57

The present studies were undertaken to evaluate the histologic effects of graft-versus-host disease on the host colon after small bowel transplantation. Graft-versus-host disease was produced in six Lewis x Brown Norway F1 rats by performing vascularized, out-of-continuity small bowel transplants from parental Lewis donors. Host proximal and distal colon were sampled 14 days after operation when signs of graft-versus-host disease, including weight loss and splenomegaly, were present. Tissue was assessed histologically by blinded observer and compared to eight sham-operated controls. Three histologic features were noted to be statistically increased in diseased animals: (1) mucin loss; (2) crypt abscesses; and (3) large lymphoid aggregates in the mucosa and submucosa. These features were more commonly noted in the distal rather than the proximal colon. Another group of five grafted animals treated with cyclosporine A (10 mg/kg/day intramuscularly) still lost weight but did not display overt signs of graft-versus-host disease and had normal-sized spleens. There was normal mucin content and no evidence of crypt abscesses in these treated animals, although large lymphoid aggregates were present. It is concluded that mucin loss, crypt abscesses, and large lymphoid aggregates are characteristics of graft-versus-host disease-induced colonic injury in this model and that these changes are most evident in the distal colon. Cyclosporine A therapy does not completely reverse the histological changes of colonic graft-versus-host disease. This model may be useful in studying the mechanisms by which immune mediated colitides preferentially affect the distal colon.
 ...
PMID:Graft-versus-host disease after small bowel transplantation is associated with host colonic injury. 755 45

In this paper, we examine in a murine system whether cyclophosphamide (CY) could prevent the development of fatal GVHD and furthermore whether it could be used to treat on-going GVHD. (C57BL/6xDBA/2)F1 (BDF1) mice were injected with spleen cells from B6 donors and their thoraces were opened to mimic cardiac operation. These mice lost body weight gradually and most of them died during 2-4 weeks post-transfusion. They showed splenomegaly, thymic atrophy and marked bone-marrow aplasia. When CY was administered at 100 mg kg-1 on days 0, 2, 7 and 9, all mice were relieved of GVHD and their organs were almost free of signs of GVHD. CY (100 mg kg-1) administered on days 7 and 9 also save mice from lethal GVHD. Moreover, CY administered at a dose of 20 mg kg-1 on days 9 and 11 when GVHD became apparent was also effective. These data suggest that CY might be used as a therapeutic agent for lethal post-transfusion GVHD.
 ...
PMID:Suppressive effect of cyclophosphamide on the progression of lethal graft-versus-host disease in mice--a therapeutic model of fatal post-transfusion GVHD. 758 6


<< Previous 1 2 3 4 5 6 7 8 Next >>