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)

Microbial superantigens (SA), bound to human B cell surface MHC class II molecules, have been shown to promote direct, "cognate" interaction with SA-reactive autologous Th cells, resulting in polyclonal Ig production. To investigate the potential for microbial SA to support Th cell-dependent, Ag-specific antibody responses, we have extended our studies to the murine system. BALB/c Th cell lines (TCL), specific for either the Mycoplasma arthritis-derived SA or the Staphylococcus aureus-derived toxic shock syndrome toxin-1) were generated. These TCL cells are SA-specific, functionally noncross-reactive, and utilize distinct TCR V beta gene families. Coculture of SA-reactive TCL cells and syngeneic B cells bearing the relevant SA results in B cell proliferation and polyclonal IgM and IgG production. In contrast, Ag-specific (SRBC-specific) antibody-forming cells are only generated in cultures that also contain SRBC. Thus, microbial SA-mediated Th-B cell interactions induce both polyclonal B cell activation and provide selective help for the proliferation and/or differentiation of B cells that have encountered specific Ag. In additional studies, we determined that the in vivo administration of toxic shock syndrome toxin-1 to young, athymic (nude) BALB/c mice results in SA binding to splenic B cells, rendering these B cells effective stimulators of and targets for SA-reactive helper TCL cells. Taken together, these results demonstrate that microbial SA mediate productive Th-B cell interactions analogous to those that occur during allospecific Th-B cell interactions in vitro and GVHD in vivo. These findings are consistent with the hypothesis that microbial SA represent environmental factors that may trigger autoimmune disease in the genetically susceptible host.
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PMID:T helper cell-dependent, microbial superantigen-induced murine B cell activation: polyclonal and antigen-specific antibody responses. 183 62

The bullous diseases that are neither immune-mediated nor inherited form a heterogeneous group that may be classified according to their major histopathologic characteristics. Such a classification allows clear distinctions to be made between entities that may have clinical similarities such as staphylococcal scalded skin syndrome, toxic shock syndrome, erythema multiforme/toxic epidermal necrolysis, and acute graft-versus-host disease. Proper differentiation of these entities is critical for their study and for appropriate management.
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PMID:Bullous dermatoses associated with systemic disease. 836 42

We have utilized a severe combined immune-deficient (SCID) mouse adoptive transfer model to explore the in vivo immunostimulatory effects of bacterial superantigens (SAg). B cell reconstituted SCID recipients were treated with the Staphylococcus aureus-derived toxic shock syndrome toxin (TSST-1) alone or in conjunction with syngeneic L3T4+ TSST-1-reactive Th cells. Over several months of study, the repetitive administration of TSST-1 resulted in a prompt, transient increase in serum IgG levels. This response required both biologically active TSST-1 and Th cells. These findings demonstrate that certain bacterial SAgs can promote Th cell-dependent B cell activation and differentiation in vivo. These studies strengthen the analogy between SAg-mediated and allospecific Th-B cell interactions responsible for the autoimmune sequelae of graft-versus-host disease.
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PMID:T helper cell-dependent, microbial superantigen-mediated B cell activation in vivo. 914 83

Umbilical cord blood (CB) constitutes a promising alternative to bone marrow for allogeneic transplantation and is increasingly used because of the reduced severity of graft-versus-host disease after CB transplantation. We have compared the T-cell receptor beta chain (TCRB) diversity of CB lymphocytes with that of adult lymphocytes by analyzing the complementarity determining region 3 (CDR3) size heterogeneity. In marked contrast to adult samples, we observed bell-shaped profiles in all of the 22 functional beta-chain variable (BV) subfamilies that reflect the lack of prior antigenic stimulation in CB samples. However, the mean CDR3 size and BV usage were comparable between CB and adult samples. BJ2 (65%) segments were used preferentially to BJ1 (35%), especially BJ2S7, BJ2S5, BJ2S3, and BJ2S1, in both CB and in adult lymphocytes. We therefore conclude that although naive as reflected by the heterogeneity of the CDR3 size, the TCRBV repertoire appears fully constituted at birth. The ability to expand TCRB subfamilies was confirmed by stimulation with staphylococcal superantigens toxic shock syndrome toxin-1 and staphylococcal enterotoxin A. This study provides the basis for future analysis of the T-cell repertoire reconstitution following umbilical CB transplantation.
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PMID:The umbilical cord blood alphabeta T-cell repertoire: characteristics of a polyclonal and naive but completely formed repertoire. 941 3

Toxic epidermal necrolysis is a drug-induced, rare, but life-threatening skin eruption. The main differential diagnoses are drug-induced erythema (hypersensitivity syndrome), acute graft-versus-host disease, staphylococcal scalded skin syndrome, and toxic shock syndrome. Because the therapy for toxic epidermal necrolysis and acute graft-versus-host disease differs largely from the others, it is necessary to make an accurate diagnosis. In addition to a detailed medical history, skin biopsy is mandatory because the skin eruptions are not always unequivocal. Discontinuation of the causing agent is crucial, and treatment in specialized intensive care units or burn units is supportive. Currently there is no specific treatment for toxic epidermal necrolysis. Advantages from corticosteroids, plasmapheresis, intravenous immunoglobulin, cyclophosphamide, cyclosporin, and N-acetylcysteine still remain to be established by controlled trials, or have failed to prove a benefit (thalidomide). The patient presented here demonstrates the difficulties in diagnosing toxic epidermal necrolysis in a critically ill patient. A short overview of the pathogenesis and the management of toxic epidermal necrolysis is provided.
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PMID:Toxic epidermal necrolysis after phenytoin usage in a brain trauma patient. 1217 97

In bone marrow-transplanted patients, chronic graft-versus-host disease is a complication that results from the persistent stimulation of recipient minor histocompatibility Ag (mHA)-specific T cells contained within the graft. In this study, we developed a mouse model where persistent stimulation of donor T cells by recipient's mHA led to multiorgan T cell infiltration. Exposure to systemic mHA, however, deeply modified T cell function and chronically stimulated T cells developed a long-lasting state of unresponsiveness, or immune adaptation, characterized by their inability to mediate organ immune damages in vivo. However, analysis of the gene expression profile of adapted CD4+ T cells revealed the specific coexpression of genes known to promote differentiation and function of Th1 effector cells as well as genes coding for proteins that control T cell activity, such as cell surface-negative costimulatory molecules and regulatory cytokines. Strikingly, blockade of negative costimulation abolished T cell adaptation and stimulated strong IFN-gamma production and severe multiorgan wasting disease. Negative costimulation was also shown to control lethal LPS-induced toxic shock in mice with adapted T cells, as well as the capacity of adapted T cells to reject skin graft. Our results demonstrate that negative costimulation is the molecular mechanism used by CD4+ T cells to adapt their activity in response to persistent antigenic stimulation. The effector function of CD4+ T cells that have adapted to chronic Ag presentation can be activated by stimuli strong enough to overcome regulatory signals delivered to the T cells by negative costimulation.
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PMID:Reviving function in CD4+ T cells adapted to persistent systemic antigen. 1973 16