Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report characterization of CD45 isoforms expressed by CD8+ lymphocytes in peripheral blood and in the graft of 40 kidney transplanted patients who underwent kidney biopsy on the basis of clinical signs suggesting rejection. Standard histological examination of the biopsy fragments and three-color cytofluorimetric analysis of lymphocytes extracted from the same fragments by mechanical and enzymatic treatment were performed simultaneously and compared to the peripheral blood lymphocytes. In 14/40 biopsies where lymphocyte extraction succeeded, the predominant subset was CD8 (CD4/CD8 mean ratio was 0.53). Almost all CD8+ cells were activated: among these CD8+ cells, 55 percent were HLA-DR+, and 68 percent CD45RO+, i.e. of a memory cell type with cytotoxic activity. This situation resembles the in vitro observation made during mitogenic stimulation of lymphocytes by phytohemagglutinin, OKT3 or CML ("culture mixte lymphocytaire"). Beside their evident interest for the diagnosis, these data could be useful for our understanding of the physiopathology of the rejection crisis.
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PMID:[Study of CD45 isoforms on T CD8 lymphocytes, in the peripheral blood and the graft in patients after kidney transplantation]. 129 62

We analyzed the role of CD4+ and CD8+ T cells in H-2-disparate skin allograft rejection in the mutant mouse strain C.B-17/Icr scid with severe combined immunodeficiency. On the day of skin allografting, scid mice were adoptively transferred with negatively selected CD4+ or CD8+ splenocytes from normal unsensitized C.B-17/Icr mice. These populations were obtained using a double-mAb--plus--complement elimination protocol using anti-CD4 or anti-CD8 mAb that resulted in no detectable CD4+ or CD8+ cells by FACS and negligible numbers of cytolytic T lymphocytes by limiting dilution analysis in anti-CD8 treated populations. Spleen cells were removed from grafted mice at the time of rejection and were tested in vitro for antidonor reactivity in several assays: mixed lymphocyte culture, cell-mediated lympholysis, and LDA for CTL and for IL-2-producing HTL. The presence of Thy 1.2+, CD4+, or CD8+ cells was determined by FACS. All control C.B-17 mice and scid mice adoptively transferred with nondepleted CD4+, and CD8+ cells rejected skin allografts with similar mean survival times (15.6 +/- 1.5, 18.8 +/- 3.4, 18.0 +/- 5.4, respectively), whereas control scid mice retain skin allografts indefinitely (all greater than 100 days). C.B-17 syngeneic grafts survived indefinitely in all groups. At the time of rejection, splenocytes from scid mice receiving CD4+ cells had negligible donor-specific cytotoxicity in CML and negligible numbers of CTL by LDA, but demonstrated a good proliferative response in MLC and IL-2-producing cells by LDA (frequency = 1/1764). There were no detectable CD8+ cells present by FACS analysis. Conversely, splenocytes from scid mice adoptively transferred with CD8+ cells had strong donor-specific cytotoxicity in CML (58.8% +/- 16.1%) and CTL by LDA (frequency = 1/3448), but no significant proliferation was detected in MLC. There were no detectable CD4+ cells by FACS, but there were small numbers of IL-2-producing cells by LDA (frequency = 1/10,204). These data demonstrate that CD4+ cells adoptively transferred into scid mice are capable of mediating skin allograft rejection in the absence of any detectable CD8+ cells or significant functional cytolytic activity. The adoptive transfer of CD8+ cells also results in skin allograft rejection in the absence of detectable CD4+ cells. The detection of small numbers of IL-2 secreting cells in these mice may indicate that CD(8+)-mediated allograft rejection in this model is dependent on IL-2-secreting CD8+ cells.
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PMID:Mediation of skin allograft rejection in scid mice by CD4+ and CD8+ T cells. 135 12

A single intravenous injection of 1 ml freshly heparinized donor blood seven days before transplantation significantly prolonged the survival of subsequent donor-specific hepatic allografts in the fully allogeneic ACI(RT1a-to-LEW(RT1l)) rat combination. The time course of cell-mediated lympholysis was studied in this animal model. The activity of CML in lymphocytes infiltrating into the hepatic allograft (CML-G) and in the spleen (CML-S) was determined by measuring % lysis of donor Con A blast cervical lymph node cells. Preoperative DST resulted in an increased activity of CML-S with a peak (31.6%, E/T = 150) on day 7. This increased CML-S activity after DST rapidly declined during the first days following hepatic transplantation. The activities of both CML-S and CML-G then increased after transplantation and reached peaks on days 15 (48%, E/T = 150) and 20 (2.57%, E/T = 75), respectively. These were much higher than the peak values of CML-S (11.2%, E/T = 150) on day 7 and CML-G (19.5%, E/T = 75) on day 6 in untreated controls and were followed by a subsequent gradual decrease in those activities to preoperative levels by day 113 posttransplant. Phenotypic analysis of lymphocytes infiltrating grafts in DST-treated hosts demonstrated that the CD4/CD8 ratio remained relatively constant (less than 1.0). While the ratio in control grafts increased and reached a peak (2.17) on day 9. Histological examination revealed that mononuclear cell infiltration of grafts reached a peak on day 9 in both DST-treated hosts and controls. This mononuclear cell accumulation gradually subsided in DST-enhanced grafts. The mitotic index of graft hepatocytes reached a peak on day 15 in DST-treated hosts and on day 7 in control. The evidence of prolonged survival of hepatic grafts in recipients pretreated with DST, despite the presence of cytotoxic T cells with increased CML activity in vitro, suggests that effector cytotoxic cell activity may not be necessary for rat liver allograft rejection and that there may be limitations in measuring host cytotoxic activity simply by CML assays.
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PMID:The time course of cell-mediated lympholysis in rat hepatic allograft recipients pretreated with a single donor-specific blood transfusion. 141 34

The negative impact of donor marrow T lymphocyte depletion on relapse of chronic myeloid leukaemia (CML) following bone marrow transplantation strongly suggests that the leukaemia is particularly susceptible to immune regulation. The immune response to CML may be mediated by major histocompatibility (MHC) locus unrestricted natural killer and lymphokine activated killer cells, or by MHC-restricted CD4 and CD8 lymphocytes. Interaction with the leukaemia is both by direct cell-contact cytotoxicity, and indirectly via cytokines and growth factors. T4 and T8 lymphocytes recognize a spectrum of minor histocompatibility antigens on the leukaemia cell which may be non-specific, leading to graft-versus-leukaemia and graft-versus-host reactions, or present only on myeloid cells leading to a tissue restricted response. The possibility that the P210 protein derived from the BCR/ABL fusion gene on chromosome 22 leads to the presentation via MHC molecules of leukaemia-specific peptide antigens is currently under investigation. Developments in understanding the immune response to CML open up the possibility of developing leukaemia-specific immunotherapy strategies.
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PMID:Immune responses to chronic myeloid leukaemia. 161 13

A new cell line designated JA-CML was derived from the peripheral blood of a patient with blastic phase CML. Sequential evolution of phenotypic and genetic markers was demonstrated during adaptation from primary to continuous culture in vitro. In the primary sample the majority of blast cells displayed the early T-cell markers, CD7, HLA-DR, and TdT, but were negative for the common ALL antigen (CALLA), CD4 and CD8. Simultaneously, unstimulated metaphase cells showed great karyotypic variation with a range of 43-46 chromosomes per cell. Clonal changes included the Ph chromosome t(9;22), loss of the Y and gain of several altered chromosomes. The cells grew slowly in suspension during the first 10 weeks of culture. During that time, cells still expressed the CD7 and HLA-DR antigens. Karyotypic analysis at ten weeks showed a pattern of 46,X,-Y,t(9;22),+8 in more than 90% of metaphases with disappearance of all other abnormal chromosomes noted in the original sample. A tetraploid subline exhibiting duplication of most chromosomes, including the Ph, comprised the remaining metaphases. Upon further cultivation in vitro, the cells transformed spontaneously over a period of several weeks, from T-lymphoid into myeloid cells. Expression of CD7 was lost, but reactivities with monoclonal antibodies to CD34, CD33 and CD13 were newly acquired. The karyotype was hypertriploid and all cells carried two copies of t(9;22) and lacked normal copies of No. 9 or Y. The cells have since maintained stable cytogenetic and phenotypic profiles. Molecular rearrangement of the breakpoint cluster region was identified in the primary blasts and the established line and T-cell receptor gene rearrangements were not found. These observations suggest that the leukemic blast arose from primitive stem cells, not irreversibly committed T cells, and that these stem cells retained the capacity to differentiate along the myeloid pathway.
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PMID:Emergence of myeloid stem cell line from T-lymphoid blastic phase of chronic myeloid leukemia in culture. 162 78

Twenty cases of myelodysplastic syndrome (MDS) were treated with ubenimex. Seventeen cases were treated with the drug over 90 d. Among these, 10 showed improvement of anemia, 12 an increase in platelet count which had decreased before treatment and 10 an increase in neutrophil count; however, 14 showed an increase in blast percentage in bone marrow aspirate. CD4/CD8 ratio was increased in 4 cases and shifted to a normal from an abnormal range in 6 cases. When the MDS cases were observed in refractory anemia (RA) and refractory anemia with excess blasts (RAEB), great improvement was seen, but in RAEB increase in blast percentage was also observed. CD4 increased mostly in RA and CD8 increased in RAEB. Ten cases of chronic myelocytic leukemia (CML) were first treated with ubenimex and cytostatics, then with ubenimex only. Six cases attained partial remission within 3 months, but one case showed a marked increase in white cell count and blast count and in another case a progression of splenomegaly associated with increase in white cell count. From these findings we conclude that ubenimex could be utilized in MDS or CML if the patient was at risk for strong chemotherapy.
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PMID:Effects of ubenimex, a biological response modifier, on myelodysplastic syndrome and chronic leukemia. 191 74

Donor-specific blood transfusion prolongs survival of fully allogeneic ACI (RT1a) renal grafts in PVG (RT1a) recipients from 6-8 days to greater than 100 days. To determine how DSBT alters effector cytotoxic cell responses, we tested freshly isolated peripheral blood lymphocytes, spleen cells, and graft infiltrating cells (GIC) from pairs of PVG recipients of ACI kidneys pretreated with DSBT or autologous blood transfusion (ABT) for cell-mediated lympholysis, antibody-dependent cellular cytotoxicity (ADCC), and natural killer activity at the day of transplantation (day 0) and days 3 and 6 posttransplantation. PBL and GIC from the same pairs of animals were examined for their phenotypic profile (CD4, CD8, 3.2.3 NK cell marker, IL-2 receptor). CML, ADCC, and NK activity were higher in PBL than splenocytes of GIC of both ABT and DSBT groups at all time points examined. CML activity of PBL at day 3 was significantly higher in DSBT vs. ABT recipients (P less than 0.01), while at day 6 both groups were equally elevated. Splenocytes demonstrated significantly lower CML activity in DSBT vs. ABT recipients at day 6 (P less than 0.05). CML activity of GIC eluted from ABT and DSBT kidneys was not detected at day 3, but was significantly elevated and equivalent in both groups at day 6. ADCC and NK activities of PBL did not differ between ABT and DSBT groups, and were negligible in splenocytes. GIC demonstrated higher NK activity in DSBT vs. ABT recipients at day 3 (P less than 0.05), while ADCC activity was not detectable at any time in either group. Phenotypic analysis of PBL and GIC at day 3 showed no significant differences between ABT and DSBT groups in the percentage of CD4 or CD8 cells. However, in both ABT and DSBT groups the ratio of CD4:CD8 cells was markedly lower in GIC than PBL. By day 6, PBL from both ABT and DSBT groups showed equivalent and significant decreases in CD4+ cells and increases in CD8+ and 3.2.3+ (NK) cells. The percentage of IL-2R+ cells remained low (less than 5%) in both groups at day 3. In contrast, at day 6 there was a significant increase in IL-2R+ (and to a lesser extent CD4+) GIC in ABT- but not DSBT-treated recipients, while CD8+ cells were significantly increased in both groups.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effects of donor-specific blood transfusion enhancement of rat renal allografts on cytotoxic activity and phenotypes of peripheral blood lymphocytes, splenocytes, and graft-infiltrating cells. 199 42

Fractionated total body irradiation was given to a patient with chronic myeloid leukemia as part of a conditioning regimen for bone marrow transplantation. The radiation treatment was discontinued after the third fraction (total dose: 385 cGy) and no bone marrow graft was given because of the patient's refusal. Peripheral blood lymphocyte levels were monitored for 3 months and lymphocyte subsets up to 50 days post-irradiation. Lymphocyte numbers reached the nadir 48 h after the last fraction and lymphopenia was still present 3 months later. All lymphocyte subsets (T, B, CD4 and CD8 cells) showed a similar decrease except for natural killer cells which exhibited a larger decline. The regenerative capacity of T cells, CD4 subset and natural killer cells was less than that of B cells and CD8 lymphocyte subsets.
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PMID:Blood cell kinetics after a 385 cGy total body irradiation given to a CML patient for bone marrow transplantation. 207 Jan 39

To assess how the immunological events occur in the colonic mucosa in patients with ulcerative colitis, it is thought to be important to evaluate the subpopulations and/or subsets of mucosal lymphocytes. In this point of view, we assayed those by lymphocyte isolation techniques and two color flow cytometry. Although our results showed no disease-specific abnormalities of the percentages of CD3, CD4, CD8, CD20, and HLA-DR (+) cells in PBL (peripheral blood lymphocyte) nor CML (colonic mucosal lymphocyte), these subsets of CML appeared to be altered according to the grade of severity of inflammation. In our cases, the HLA-DR (+) cell and CD4 population were larger in severely inflamed mucosa. Furthermore, fluorescence intensities of HLA-DR antigen of CD20 population in CML were greater than those in PBL. These results suggest that the B cell-mediated mechanisms may play an important role in maintaining the severe inflammation, and the clinical significance of these studies are discussed.
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PMID:[Analysis of subsets of colonic mucosal lymphocyte in ulcerative colitis by two color flow cytometry]. 225 Mar 91

In vivo administration of an anti-interleukin-2 (anti-IL-2) receptor monoclonal antibody is a potential new therapy for prevention of allograft rejection of a freshly transplanted organ. Such an approach is more selective than targeting all T cells, or even the CD4 or CD8 major subsets, because only the very recently activated cells should be affected. A clinical trial of anti-Tac monoclonal antibody is in progress in which 20 mg of the immunoglobulin G 2a (lgG2a) antibody is administered intravenously daily for 10 days after cadaveric renal transplantation. Combinations with and without azathioprine, and with varying doses of cyclosporine with prednisone, are being evaluated in a randomized trial. Results to date show a significant immunosuppressive effect of anti-Tac, as measured by a reduced incidence and later onset of acute rejection episodes compared with cyclosporine plus prednisone or cyclosporine plus azathioprine plus prednisone. Removal or cytodestruction of IL-2-receptor positive cells from the peripheral blood does not occur to any major degree, even though serum levels of the antibody are always detectable. In addition, functional studies of MLR, CML, and suppressor cell generation 4 days after cessation of anti-Tac administration show no significant difference between treated and control groups The effect of anti-Tac seems, therefore, to be limited to inhibition of IL-2-mediated T-cell growth during the period of administration, with recovery after a few days' lag period.
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PMID:Prophylactic use of monoclonal anti-IL-2 receptor antibody in cadaveric renal transplantation. 268 58


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