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)

Oral mucosal biopsies of 12 allogeneic marrow transplant recipients with chronic graft-versus-host disease (GVHD) involving the mouth were compared with biopsies taken before transplantation. They were also compared with biopsies from otherwise healthy patients with oral lichen planus, and with those from a control group of normal individuals. Biopsies from chronic GVHD exhibited a low number of infiltrating T lymphocytes (CD3 cells) compared with those from oral lichen planus, which showed intense cell infiltration (p less than 0.005). The ratio of CD4 to CD8 cells in biopsies taken after the manifestation of chronic GVHD exhibited no consistent variation compared with those taken before transplantation or with biopsies of oral lichen planus. The CD4/CD8 ratio in all groups investigated varied between 4:1 and 6:1. The number of natural killer cells (CD57), was increased in biopsy specimens taken before transplantation compared with the other groups. The frequency of homing receptor, Leu-8 bearing T cells was low in the biopsy specimens of all groups, compared with the corresponding frequency in peripheral blood (10-45 and 60-90%, respectively; p less than 0.001). In the biopsies from chronic GVHD and oral lichen planus the number of lymphocytes with transferrin receptors was increased compared with the pretransplant and control groups. Virtually no infiltrating cells were carrying interleukin-2 receptors (CD25) in any of the groups studied. Langerhans cells (CD1) were more frequently found in the specimens from chronic GVHD and oral lichen planus than in the pretransplant specimens and the control group (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparative immunological analysis of the oral mucosa in chronic graft-versus-host disease and oral lichen planus. 135 59

The circulating lymphocytes of 88 consecutive patients following autologous, conventional, or T-cell depleted bone marrow transplantation were serially analyzed for B-cell surface antigen expression and function. In the majority of patients, except for those who developed chronic graft-versus-host disease, the number of circulating CD20+ B cell normalized by the fourth posttransplant month. The earliest detectable B cells normally expressed HLA-DR, CD19, surface immunoglobulin (slg), CD21, Leu-8, and lacked expression of CD10 (CALLA). In addition, the circulating B cells expressed CD1c, CD38, CD5, and CD23 for the first year following transplant, antigens that are normally expressed on a small percentage of circulating B cells in normal adults, but highly expressed on cord blood B cells. Similar to cord blood B cells, patient B cells isolated during the first year following transplant, proliferated normally to Staphylococcus aureus Cowan strain I (SAC), and produced IgM, but minimal or no IgG when stimulated with pokeweed mitogen and SAC, unlike normal adult B cells that produce both. The similar phenotype and function of posttransplant and cord blood B cells, and their similar rate of decline in patients and normal children adds further evidence to support the hypothesis that B-cell differentiation posttransplant is recapitulating normal B-cell ontogeny.
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PMID:B-cell differentiation following autologous, conventional, or T-cell depleted bone marrow transplantation: a recapitulation of normal B-cell ontogeny. 169 84

Despite complete matching of siblings for the HLA loci, after bone marrow transplantation (BMT), approximately 20% develop graft-versus-host disease (GVHD). This is presumably due to incompatibility of minor histocompatibility antigens (mHa). We investigated the polymorphisms of 14 adhesion molecules (CD2, CD28, CD31, CD34, CD36, CD42, CD44, CD48, CD49b, CD54, CD62L, CD86, CD102, and CD106) in Japanese subjects and their association with the occurrence of GVHD after allogeneic HLA identical BMT. Six molecules (CD2, CD31, CD42, CD49b, CD54, and CD62L), which were found to be polymorphic, were then examined in 118 HLA identical sibling donors and recipients who had undergone BMT. Association of the incompatibility of the polymorphic molecules with the presence or absence of GVHD was examined. In these six, we observed a significant correlation between acute GVHD and the compatibility of CD31 (codons 563/670) (Pcorrected = .018), and CD31 (codons 563/670) + CD62L (Pcorrected = .018) in patients with the HLA-B44-like superfamily. In patients with the HLA-A3-like superfamily, the compatibility of CD62L (Pcorrected = .03) and CD62L + CD49b (P = . 004, Pcorrected = .078) was associated with acute GVHD. Therefore, CD31, CD49b, and CD62L might be candidates for immunodominant mHa.
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PMID:Evidence that CD31, CD49b, and CD62L are immunodominant minor histocompatibility antigens in HLA identical sibling bone marrow transplants. 973 Oct 77

To determine whether administration of G-CSF induces phenotypic or functional changes in T cells, we examined peripheral blood T cells from normal individuals receiving G-CSF for activation antigen and adhesion molecule expression before and after G-CSF administration. G-CSF (10 microg/kg/day) was administered subcutaneously to 14 normal individuals for 3-5 days and their PBMC were serially analyzed with monoclonal Ab (mAb) directed to HLA-DR, CD45RO, CD45RA, CD25, CD122, CD95, CD11a, CD49d, CD44 and CD62L (L-selectin) coupled with anti-CD3 mAb. Among T cells positive for these antigens, only the proportion of T cells expressing L-selectin significantly decreased from 68% to 37% after 3-day G-CSF administration. When peripheral blood CD3+ T cells obtained before and after G-CSF administration were sorted into two populations depending on the expression of L-selectin and tested for their proliferative response to allogeneic B cells, the reactivity of L-selectin- cells to alloantigen stimulation was consistently lower than that of L-selectin+ cells regardless of the exposure to G-CSF. The decrease in the relative number of L-selectin+ cells induced by G-CSF administration may contribute to the unexpectedly low incidence of severe acute GVHD after allogeneic PBSC transplantation.
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PMID:Administration of G-CSF to normal individuals diminishes L-selectin+ T cells in the peripheral blood that respond better to alloantigen stimulation than L-selectin- T cells. 1019 95

Transfusion or transplantation of T lymphocytes into an allogeneic recipient can evoke potent immune responses including, in immunocompromised patients, graft-versus-host disease (GVHD). As our previous studies demonstrated attenuated immunorecognition of red blood cells covalently modified with methoxy(polyethylene glycol) (mPEG), we hypothesized that T-cell activation by foreign antigens might similarly be prevented by mPEG modification. Mixed lymphocyte reactions (MLR) using peripheral blood mononuclear cells (PBMC) from HLA class II disparate donors demonstrate that mPEG modification of PBMC effectively inhibits T-cell proliferation (measured by (3)H-thymidine incorporation) in a dose-dependent manner. Even slight derivatization (0.4 mmol/L mPEG per 4 x 10(6) cells) resulted in a >/=75% decrease, while higher concentrations caused >/=96% decrease in proliferation. Loss of PBMC proliferation was not due to either mPEG-induced cytotoxicity, as viability was normal, or cellular anergy, as phytohemagglutinin (PHA)-stimulated mPEG-PBMC demonstrated normal proliferative responses. Addition of exogenous interleukin (IL)-2 also had no proliferative effect, suggesting that the mPEG-modified T cells were not antigen primed. Flow cytometric analysis demonstrates that mPEG-modification dramatically decreases antibody recognition of multiple molecules involved in essential cell:cell interactions, including both T-cell molecules (CD2, CD3, CD4, CD8, CD28, CD11a, CD62L) and antigen-presenting cell (APC) molecules (CD80, CD58, CD62L) likely preventing the initial adhesion and costimulatory events necessary for immune recognition and response.
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PMID:Stealth cells: prevention of major histocompatibility complex class II-mediated T-cell activation by cell surface modification. 1047 44

Umbilical cord blood (CB) transplantations are associated with a lower risk of severe graft-versus-host disease (GVHD) compared to BMT. GVHD is an immune reaction that involves interaction between cell surface molecules resulting in cell activation and release of many cytokines. Monocytes are known to be an important source of cell adhesion (CAM) and co-stimulatory molecules which play a crucial role in the efficient activation of T and B cells. We analyzed the phenotype of CB monocytes in the presence or absence of an inflammatory signal (rIFN-gamma) and compared them to adult blood (AB); the expression of HLA-DR and 17 different markers (CD11a, CD11b, CD11c, CD18, CD29, CD40, CD44, CD49a, CD49d, CD49e, CD49f, CD54, CD58, CD62L, CD80, CD86 and CD102) was measured by flow cytometry. Statistical analysis showed that, compared to AB, CB monocytes did not express CD11b, CD11c, CD49d and after stimulation with rIFNgamma, they lost the expression of CD58 and CD102, whereas CD80 and CD86 expression was induced. The analysis of fluorescence intensity (MFI) revealed that CB monocytes expressed some CAM (CD29, CD54, CD102) with a lower intensity than AB monocytes except CD44. In conclusion, absence and reduced expression of some markers argue for a different phenotypic profile of CB monocytes compared to AB monocytes, which might partly contribute to their impaired immune response and to the low incidence of GVHD observed after CB transplantations. However, CB monocytes expressed CD80 and CD86 co-stimulatory molecules, but this expression did not prove a normal co-stimulatory function.
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PMID:Expression of HLA-DR, CAM and co-stimulatory molecules on cord blood monocytes. 1116 18

After non-T-cell-depleted allogeneic hematopoietic stem cell transplantation (HSCT), both alloreactive and homeostatic signals drive proliferation of donor T cells. Host-reactive donor T cells, which proliferate on alloantigen stimulation, are responsible for the life-threatening graft-versus-host disease. Non-host-reactive donor T cells, which proliferate in response to homeostatic signals, contribute to the beneficial peripheral T-cell reconstitution. The elimination of alloreactive T cells is a major therapeutic challenge for HSCT and would greatly benefit from their specific identification. After T-cell transfer in lymphopenic recipients, the present results show that alloreactive T cells rapidly divided; up-regulated CD69, CD25, and CD4 molecules; and down-regulated CD62L. In contrast, nonalloreactive T cells started to divide later and did not up-regulate CD69, CD25, and CD4. Thus, these 2 cell populations can be effectively discriminated. This should facilitate the specific depletion of alloreactive T cells in allogeneic HSCT.
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PMID:Division rate and phenotypic differences discriminate alloreactive and nonalloreactive T cells transferred in lethally irradiated mice. 1846 12

The "conventional" NK1.1(-) T cells from mouse blood and marrow were compared with regard to surface receptors, cytokine secretion, and function. Most blood NK1.1(-) CD4(+) and CD8(+) T cells expressed the naive CD44(int/lo)CD62L(hi)CD45RB(hi) T-cell phenotype typical of those in the peripheral lymphoid tissues. In contrast, most marrow NK1.1(-) CD4(+) and CD8(+) T cells expressed an unusual CD44(hi)CD62L(hi)CD45RB(hi) phenotype. The blood NK1.1(-) CD4(+) T cells had a naive T-helper cytokine profile and a potent capacity to induce lethal graft versus host (GVH) disease in a C57BL/6 donor to a BALB/c host bone marrow transplantation model. In contrast, the marrow NK1.1(-) CD4(+) T cells had a Th0 cytokine profile and failed to induce lethal GVH disease, even at 20-fold higher numbers than those from the blood. NK1.1(-) CD8(+) T cells from the blood but not the marrow induced lethal GVH disease. Nevertheless, the marrow NK1.1(-) CD8(+) T cells induced potent antitumor activity that was augmented by marrow NK1.1(-) CD4(+) T cells and facilitated hematopoietic progenitor engraftment. The inability of marrow CD4(+) and CD8(+) T cells to induce GVH disease was associated with their inability to expand in the blood and gut of allogeneic recipients. Because neither the purified marrow CD4(+) or CD8(+) T cells induced GVH disease, their unique features are desirable for inclusion in allogeneic bone marrow or hematopoietic progenitor transplants.
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PMID:Unique patterns of surface receptors, cytokine secretion, and immune functions distinguish T cells in the bone marrow from those in the periphery: impact on allogeneic bone marrow transplantation. 1183 Apr 99

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation (alloSCT). Donor T cells that accompany stem cell grafts cause GVHD by attacking recipient tissues; therefore, all patients receive GVHD prophylaxis by depletion of T cells from the allograft or through immunosuppressant drugs. In addition to providing a graft-versus-leukemia effect, donor T cells are critical for reconstituting T cell-mediated immunity. Ideally, immunity to infectious agents would be transferred from donor to host without GVHD. Most donors have been exposed to common pathogens and have an increased precursor frequency of memory T cells against pathogenic antigens. We therefore asked whether memory CD62L-CD44+ CD4+ T cells would induce less GVHD than unfractionated or naive CD4+ T cells. Strikingly, we found that memory CD4 cells induced neither clinical nor histologic GVHD. This effect was not due to the increased number of CD4+CD25+ regulatory T cells found in the CD62L-CD44+ fraction because memory T cells depletion of these cells did not cause GVHD. Memory CD4 cells engrafted and responded to antigen both in vivo and in vitro. If these murine results are applicable to human alloSCT, selective administration of memory T cells could greatly improve post-transplant immune reconstitution.
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PMID:Memory CD4+ T cells do not induce graft-versus-host disease. 1284 55

The major challenge in allogeneic hematopoietic cell transplantation is how to transfer allogeneic T-cell immunity without causing graft-versus-host disease (GVHD). Here we report a novel strategy to selectively prevent GVHD by depleting CD62L(+) T cells (naive and a subset of memory T cells). In unprimed mice, CD62L(-) T cells (a subset of memory T cells) failed to proliferate in response to alloantigens (which the mice have never previously encountered) and were unable to induce GVHD in allogeneic hosts. CD62L(-) T cells contributed to T-cell reconstitution by peripheral expansion as well as by promoting T-cell regeneration from bone marrow stem/progenitor cells. CD62L(-) T cells from the animals previously primed with a tumor cell line (BCL1) were able to inhibit the tumor growth in vivo but were unable to induce GVHD in the third-party recipients. This novel technology may allow transfer of allogeneic recall antitumor and antimicrobial immunity without causing GVHD.
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PMID:Transfer of allogeneic CD62L- memory T cells without graft-versus-host disease. 1455 Nov 32


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