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)

In order to understand the mechanism of immunosuppression caused by infusion of placental gamma globulin (PGG) in patients with renal allografts, rheumatoid arthritis, and graft-versus-host disease (GVHD) following bone marrow transplantation (BMT), we have examined the effect of PGG in vitro and in a model of the xenogeneic, local graft-versus-host reaction (LGVHR). PGG inhibited lymphocyte proliferation in mixed lymphocyte cultures (MLC) (P less than 0.005) and depressed interleukin-2 (IL-2) levels in such cultures at 72 hours (P less than 0.01). In contrast phytohemagglutinin (PHA)- and pokeweed mitogen (PWM)-induced T and B lymphocyte blastogenesis was not affected by such PGG treatment. PGG neither decreased the [3H] TdR pulse incorporation in unstimulated lymphocytes nor affected cell viability. Cell cycle analysis by flow cytometry showed that PGG reduced the percentage of cells in S and G2, M phases during the MLC, but did not alter cell cycling during PWM-stimulated proliferation. An immunosuppressive effect of PGG on the LGVHR was tested in a model of intracutaneous transplantation of PGG-treated human lymphocytes into cyclophosphamide-immunosuppressed rats. Lymphoprep-separated human tonsillar lymphocytes were incubated with RPMI-1640 buffer containing: (1)PGG, 4 mg/ml, (2) human plasma albumin, 4 mg/ml, (3) mitomycin-C, 25 micrograms/ml, or (4) no additive. Cells of each preparation (3 X 10(7) cells in 0.1 ml) were injected intracutaneously into cyclophosphamide-treated male rats at separate abdominal locations. A fifth site received only the buffer solution. Five days after injection of cells, each rat received [125I]UdR (10 muCi) intraperitoneally and was killed after 5 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activity of human placental gamma globulin in blocking immune functions in vitro and in abrogating the xenogeneic, local graft-versus-host reaction. 248 43

Gestation can induce a priming for a GVHR towards paternal strain antigens, although this priming is significantly lower than the one induced by experimental immunization. A role has been sought for placental substances in decreasing this priming through immunomodulation. BALB/c (H-2d) spleen cells do not usually induce a systemic, lethal GVHR in DBA/2 (H-2d) newborn mice except when the donors are preimmunized with DBA/2 cells. Placental extracts (as well as RPMI medium or liver extracts used as controls) were added to DBA/2 cells injected into BALB/c mice used as cell donors for GVH induction. The latter's spleen cells, harvested on day 6 after immunization, were used for systemic and local GVHR. In the systemic assay (lethal effect on DBA/2 newborn mice injected i.v. with BALB/c spleen cells) a significant protection was observed. In the local assay (popliteal lymph node assay in F1 hybrids injected with BALB/c spleen cells into the foot-pad) a highly significant inhibition of priming was detected in recipients injected with spleen cells from placental extract-treated donors. The stimulation index was even lower than that obtained with unprimed BALB/c spleen cells. The same type of local GVHR in (CBA/Ca X A/J) F1 hybrids injected with CBA cells led to similar results. In both situations (systemic and local GVHR) the observed inhibition was found to be specific to the priming cell strain. These results support the working hypothesis that placental substances are able to modify the systemic response of an organism towards both H-2 and non-H-2 alloantigens.
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PMID:Maternal alloimmune reactions towards the murine conceptus and graft-versus-host reaction (GVHR). II. Inhibition of priming by placental extracts. 374 78

To explore the effect of bone marrow camouflaged with methoxy polyethylene glycol (mPEG) on allogeneic bone marrow transplantation, 60 BALB/c(H-2d) mice were randomly divided into 3 groups after irradiation by 8.0 Gy of (60)Co gamma ray. A group was given RPMI 1640 0.5 ml in tail vein. B group was infused with the bone marrow cells (1 x 10(7)) mixed with the spleen cells (1 x 10(7)) of donor 615(H-2k) mice. C group was transplanted with same dose cells, which were camouflaged with mPEG before infusion. Severity GVHD was determined by total manifestation of mice, survival rate, survival time and histo-pathological microscopy, and engraftment of allogeneic bone marrow was evaluated by chromosome examination. The results showed that 75% mice in B group had severe adverse manifestations, such as hunched posture, diarrhea and loss of hair. Occurrence of the same adverse manifestations in C group was 35% and significantly lower than that in B group (P <or= 0.05). The mean survival time and survival rate of C group were 16.1 days and 50% respectively, which were higher than those of B group (12.1 days and 20%). White blood cells in peripheral blood of C group mice recovered more quickly than that in B group mice. The number of GVHD grad III in B group was 59%, whereas in C group was 20% (chi(2) = 3.844, P = 0.050); allogeneic bone marrow was successfully engrafted in B and C groups. In conclusion, GVHD of allogeneic bone marrow transplantation can be alleviated by bone marrow cells camouflaged with mPEG, and such transplantation may be able to prolong survival time and increase survival rate.
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PMID:[Study on bone marrow transplantation camouflaged with methoxy polyethylene glycol]. 1597 31

In order to explore the influence of purified donor regulatory T cells (T(Reg) cells) infused after allogeneic bone marrow transplantation (allo-BMT) on GVHD and hematopoietic reconstitution of mice, an allo-BMT model of C(57)BL/6-->BALB/c mice was established. CD4(+)CD25(+)T(Reg) cells were purified through bead-magnetic activated cells separated from donor mice peripheral blood. The recipient mice were randomly divided into three groups: CD4(+)CD25(+) T cells, CD4(+)CD25(-) T cells and RPMI 1640 culture medium. These cells and RPMI 1640 were infused into recipient mice by caudal veins at about 6 to 8 hours after allo-BMT respectively. Incidence of GVHD, pathological lesion of liver, spleen, small intestine, survival time and hematopoietic reconstitution in the recipients were observed after allo-BMT. The results showed that the time for WBC > 1.0 x 10(9)/L was (8.14 +/- 3.26) days, (17.62 +/- 5.71) days, (19.81 +/- 6.77) days and the time for Plt > 20.0 x 10(9)/L was (5.29 +/- 1.34) days, (8.97 +/- 3.44) days, (9.52 +/- 3.92) days in T(Reg) positive cell group, T(Reg) negative cell group and the blank control group respectively, and the recovery times of WBC and Plt in T(Reg) positive cell group were faster than that in T(Reg) negative cell group and the blank control group (P < 0.05). The scores of GVHD were (1.33 +/- 0.58), (1.80 +/- 0.27), (1.93 +/- 0.45) in three groups of mice at about 15 days after allo-BMT, respectively, the GVHD in T(Reg) positive cell group was slighter than that in T(Reg) negative cell group and the blank control group (P < 0.05). It was found that GVHD pathologic manifestations of the liver, spleen and small intestine in T(Reg) positive cell group were slighter in a certain extent than those in other two groups at about (25 - 30) days after allo-BMT. The mean survival time in three groups was (41.45 +/- 17.88) days, (18.75 +/- 14.39) days and (25.67 +/- 16.84) days after allo-BMT, respectively, which in the T(Reg) positive cell group was significantly longer than that in other two groups (P < 0.05). It is concluded that donor-T(Reg) cell infusion can mitigate the GVHD so as to reach hematopoietic reconstitution and prolong survival time after allo-BMT in mice.
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PMID:[Influence of donor T(reg) cells on GVHD and hematopoietic reconstitution after allogeneic bone marrow transplantation in mice]. 1760 63

A recently discovered population of lymphocytes, called T regulatory cells (Tregs), is characterized by expression of transcription factor Forkhead box P3 (FoxP3). These cells have been successfully used as therapeutic treatments and prophylaxis for graft-versus-host disease (GVHD) and diabetes and might become an attractive alternative to traditional immunotherapy. Here we evaluated how the type of culture medium and the type of serum can influence yield and quality of Tregs after in vitro expansion. We compared Treg fold of expansion and their phenotypical characteristics including expression of FoxP3, CD25, CD127, CD62L and CD45RA in three commercially available culture media (RPMI 1640 (Cellgro; Manassas VA, USA), SCGM (Cellgenix; Freiburg, Germany), and X-VIVO 20 (Lonza; Walkersville, MD, USA)) with addition of human serum (HS, 10%) or fetal bovine serum (FBS, 10%). Among the tested media, X-VIVO 20 supplemented with HS produced the highest yield after 17days of in vitro expansion (a median of 86-fold expansion, range 30-1365) and highest level of FoxP3 expression (a median of 66.8% of positive cells, range 56-84.8%) in CD4(+) CD25(hi)CD127(lo/neg) FACS sorted polyclonal Tregs. There was no difference in Tregs yield whether HS or FBS serum was used. In conclusion, the yield of the ex vivo expanded Tregs is related to the type of media applied. Supplementation of the culture with FBS or human serum is equally beneficial.
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PMID:Impact of culture medium on CD4(+) CD25(high)CD127(lo/neg) Treg expansion for the purpose of clinical application. 2346 50