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)

This antigen was examined in rats of different ages (new-born, 3, 5, 7, 10, 12 and 14 days after birth and adult) by immunofluorescence and immunoelectron microscopy. Changes in each kind of salivary gland when graft versus host disease was induced in recipient rats were also investigated. Monoclonal antibodies (HAM 2 or OX 18) specific to rat MHC class I antigen were used and these were detected by FITC-conjugated anti-mouse immunoglobulin. With HAM 2, MHC class I antigen in the submandibular gland was mostly located in the secretory duct cells; this expression was first found 10 days after birth. The antigen was found on the cell surfaces of the secretory duct cells by immunoelectron microscopy. With OX 18, MHC class I antigen was mainly found in the secretory duct cells, but weak expression was also found in the acinar cells. Localization of the antigen, by HAM 2 and OX 18 was less evident in the secretory duct cells of parotid and sublingual glands. When graft versus host disease was induced, MHC class I antigen (HAM 2) was observed in both acinar and secretory duct cells of the submandibular gland.
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PMID:Analysis of major histocompatibility complex (MHC) class I antigen in the rat salivary gland. 162 41

The murine 402AX teratocarcinoma is a MHC class I antigen negative tumor of 129 strain origin. Host resistance to the 402AX tumor is genetically controlled. When passed intraperitoneally in genetically resistant mice, the tumor cells are induced to express MHC Class I antigens of the 129 genotype. When passed in genetically susceptible mice, the tumor cells remain MHC class I antigen negative. Earlier studies have demonstrated that resistance to the tumor and regulation of tumor cell MHC class I antigen expression are under the control of the host's immune system. The present studies indicate that splenic Lyt 1-, Lyt 2-, and L3T4-expressing cells regulate tumor cell MHC class I antigen expression, and that these cells require a genetically resistant host environment in which to differentiate. Splenic T cells primed to the 402AX tumor and transferred into genetically susceptible 129 mice give rise to GVHD, suggesting that immunity to the tumor involves reactivity to 129 minor histocompatibility antigens.
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PMID:402AX teratocarcinoma MHC class I antigen expression is regulated in vivo by Lyt 1, Lyt 2, and L3T4 expressing splenic T cells. 309 94

Cytomegalovirus (CMV) infection has been associated with graft rejection in solid organ transplantation and with graft-versus-host disease in marrow transplantation. We hypothesized that CMV-infected endothelial cells play an important role in the rejection process, because of their strategic localization at the interface with the host immune system and their ability to modulate T cell function. To study the effect of CMV infection on cell-mediated cytotoxicity against endothelial cells, peripheral blood mononuclear cells (MNC) were incubated with CMV-infected umbilical vein endothelial cells (CMV-UVEC) or mock-infected controls (M-UVEC) and lysis measured by [3H]leucine release. MNC lysed only CMV-UVEC to a maximum of 23% at E:T 20:1. Lysis was not affected by CD3+ cell depletion, but was abolished by CD16+ cell depletion, indicating that NK cells were the effectors. The kinetics of the NK-mediated lysis of CMV-UVEC paralleled the time course of CMV antigen expression. Furthermore, ganciclovir treatment of CMV-UVEC cultures decreased both specific antigen synthesis and NK-mediated lysis. This indicated that NK might recognize either a viral antigen or a cellular antigen modulated by CMV infection. Treatment of CMV-UVEC with F(ab)2 fragments of human polyclonal anti-CMV antibodies failed to inhibit NK cytotoxicity. In contrast, F(ab)2 fragments of MB40.5, a murine MAb reactive with a conserved epitope on the human MHC class I, significantly decreased lysis, proving that NK lysis of CMV-UVEC is an MHC class I-dependent function. To determine whether CMV-UVEC lysis was dependent solely on upregulation of MHC class I, MNC were incubated with CMV-UVEC mixed with uninfected UVEC. There was no competition for NK-target recognition sites, indicating that NK lysis required an interaction with an MHC class I antigen modified by viral infection. Antibodies against IFN-alpha or -beta did not block NK cytotoxicity against CMV-UVEC. Our findings provide a working frame for further evaluation of cellular immune responses to CMV infection.
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PMID:NK recognition of cytomegalovirus-infected endothelial cells depends on viral replication and MHC class I expression. 882 29

Bone marrow cells may be a useful vehicle for pretransplant delivery of alloantigen to induce tolerance in vivo. However, infusion of fully allogeneic bone marrow cells carries the risk of graft-versus-host disease. In order to reduce this risk while retaining the tolerogenic potential of the bone marrow infusion, we have investigated the ability of recipient bone marrow cells expressing a single donor MHC class I antigen to induce specific unresponsiveness in vivo. We show that 5x10(7) and 5x10(6) bone marrow cells from a transgenic strain of CBA mice, CBK, that express a single donor class I MHC gene, H2Kb (H2k + H2Kb), were able to induce long term survival of a fully allogeneic C57BL/10 (H2b) cardiac allograft in 80% and 20% of unmanipulated CBA (H2k) recipients, respectively, when administered intravenousely on the day of transplantation. In contrast, the same doses of fully allogeneic C57BL/10 donor bone marrow were completely ineffective at prolonging graft survival. When the interval between bone marrow infusion and transplantation was increased to 14 days, CBK bone marrow at either dose (5x10(6) and 5x10(7)) induced long term survival of C57BL/10 cardiac allografts in all recipients (MST>100 days) while fully allogeneic donor bone marrow was ineffective (MST=7, 5x10(6) cells; MST=6, 5x10(7)). Only when 27 or 42 days had elapsed between bone marrow infusion and transplantation did fully allogeneic bone marrow exert a beneficial effect on graft survival. Administration of 5x10(6) C57BL/10 bone marrow cells 27 and 42 days before transplantation resulted in long term survival of C57BL/10 hearts in 67% and 75% of CBA recipients. Next, we investigated whether manipulating the periphery of the recipient with a depleting anti-Cd4(4) monoclonal antibody before bone marrow infusion would facilitate the induction of unresponsiveness. When pretreatment with bone marrow cells was combined with anti-Cd4 monoclonal antibody 28 days before transplantation, a 10-fold reduction in the number of either C57BL/10 or CBK bone marrow cells required to induce tolerance was observed. These data confirm that bone marrow is a suitable vehicle for alloantigen delivery at the time of, or before, transplantation, on its own or in combination with anti-Cd4. The use of recipient type bone marrow cells expressing one or more donor MHC genes may be more effective than fully allogeneic, donor bone marrow cells in inducing tolerance in vivo. This difference may have important clinical implications for the current trials of donor bone marrow given at the time of transplantation in order to augment chimerism and to prolong graft survival.
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PMID:Syngeneic bone marrow expressing a single donor class I MHC molecule permits acceptance of a fully allogeneic cardiac allograft. 895 73