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)

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

Because keratinocytes (KCs) express HLA-DR in a wide variety of skin diseases in which mononuclear leukocytes are observed in close apposition to KCs (i.e., graft-versus-host disease), and since gamma interferon (IFN-gamma) induces HLA-DR expression on KCs, we asked whether IFN-gamma treatment of KCs would influence the adherence of mononuclear leukocytes. When allogeneic peripheral blood mononuclear leukocytes (PBML) and a Leu-3+ T cell clone were coincubated with IFN-gamma-treated KCs (300 U/ml, 3 days), there was a marked increase in binding compared with nontreated KCs. Similar binding results were obtained using a cutaneous squamous carcinoma cell line (SCL-1) after IFN-gamma treatment. The IFN effect was relatively specific for IFN-gamma, as neither IFN-alpha nor -beta had any effect. Tumor necrosis factor exposure (500 U/ml, 3 days) increased the binding of the Leu-3+ T cell clone to both KCs and SCL-1 cells. Neutrophils displayed a less marked (but statistically significant) increase in binding to IFN-gamma-treated KCs. Using the Leu-3+ cell clone and SCL-1 cells, detailed kinetic analysis of the effect of IFN-gamma on binding was performed. The increased adherence between the cells began to appear after only 7 hours of treatment with r-IFN-gamma (300 U/ml) and reached a plateau at 48 hours, with significantly enhanced binding continuing for at least 48 hours after removal of IFN-gamma. The mechanism of binding was explored by preincubation of the PBML/Leu-3+ T cells with anti-LFA-1 (lymphocyte function-associated antigen) antibody (0.6-6.0 micrograms/ml), which totally inhibited the binding with no effect by anti-LFA-2 or -3 or class I or II antibodies despite documented binding of these antibodies to the cells. These results suggest that, after exposure to IFN-gamma, the ability of KCs to bind mononuclear leukocytes is strongly enhanced, and this adherence may be important in leukocyte trafficking in the skin as well as contributing to altered KC-leukocyte interaction, which may be of fundamental importance in a variety of skin disease.
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PMID:Recombinant gamma interferon increases the binding of peripheral blood mononuclear leukocytes and a Leu-3+ T lymphocyte clone to cultured keratinocytes and to a malignant cutaneous squamous carcinoma cell line that is blocked by antibody against the LFA-1 molecule. 244 90

Using immunohistological techniques, the cellular composition of lymph nodes was assessed in 18 patients who had died 15 to 326 days after allogeneic bone marrow transplantation for leukaemia. The lymph nodes showed reduced cellularity of the cortex and paracortex, dilated sinuses and no lymphoid follicles. The majority of leucocytes were T lymphocytes with an inversion of the normal T4:T8 ratio. No cells were detected expressing immature cortical thymocyte antigens, using NA1/34 and OKT10, but an excess of T11 (E rosette receptor)+ cells over the sum of T4+, T8+ and HNK1+ cells raised the possibility of the presence of immature cells. B lymphocytes were extremely rare and present as clusters in only two patients. Despite this, plasma cells were prominent in many cases and their number increased with time post transplant. The predominant immunoglobulin heavy chain class was IgA in seven cases, IgG in three cases, IgM in two cases and IgE in one case with no relationship between dominant class and days post transplant. In patients with graft-versus-host disease (GvHD), there was a significantly lower T4:T8 ratio but no increase in expression of lymphocyte activation markers. Pyknotic leucocytes were present in half of the cases with GvHD and none of the other cases. No differences were detected in patients who had received marrow purged with monoclonal antibodies (Campath-I or UCHT1). Chimeric studies on three recipients of one haplotype matched marrow, using a monoclonal antibody specific for HLA-A2 and A28 antigens, showed a significant influx of donor cells by 56 days but this did not appear to be an immediate prelude to full morphological reconstitution.
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PMID:The cellular composition of human lymph nodes after allogenic bone marrow transplantation: an immunohistological study. 354 75

The cellular infiltrate in skin biopsies of 9 patients with graft-versus-host disease (GVHD) has been characterized with the use of monoclonal antibodies by indirect immunofluorescence. Most infiltrating cells in dermis reacted with monoclonal antibodies which recognize T-cell antigens. A mean of 45% of all dermal cells were T11-reactive, while a smaller proportion of cells were identified by another "pan" antibody, OKT3. In all but two instances the proportion of dermal cells reactive with OKT8 exceeded the proportion reactive with OKT4. Anti-Tac, which identifies activated T cells, reacted with a variable proportion of cells. Monocytes and null cells (OKM1+) were frequently observed but were less numerous than T-lymphocytes. Infiltrates were sparsely populated with OKT6-reactive cells, and there was no difference between the number of intraepidermal cells reactive with this antibody in study subjects and normal controls. Few cells reactive with Leu 7 (large granular lymphocytes) or with anti-B-cell reagents were seen. These findings may have clinical implications for use of monoclonal antibodies for prophylaxis and treatment of GVHD.
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PMID:Identity of immune cells in graft-versus-host disease of the skin. Analysis using monoclonal antibodies by indirect immunofluorescence. 638 61