RESUMO
The rate of capping and shedding of cross-linked surface immunoglobulins (SIg) was slower in old Lewis rats (greater than 24 mo) than in young Lewis rats (3-4 mo). Analysis of spleen cell populations with the fluorescence-activated cell sorter indicated that with aging there was a loss of cells with a high density of SIg. Cells with the highest density of SIg capped and shed cross-linked SIg faster than cells with a low density of SIg. The alteration in density of SIg may account for the difference in capping kinetics. Colchicine treatment increased the rate of capping of lymphocytes from young animals, but had no effect on the capping kinetics of lymphocytes from old animals.
Assuntos
Envelhecimento , Linfócitos B/imunologia , Capeamento Imunológico , Receptores de Antígenos de Linfócitos B/metabolismo , Animais , Colchicina/farmacologia , Endocitose , Feminino , Capeamento Imunológico/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos Lew , Baço/imunologiaRESUMO
Established subcutaneous Moloney sarcomas (MST-1) of large size and long duration were eliminated from syngeneic rats by intravenous infusion of varying numbers of specific syngeneic effector T lymphocytes. Spleen cells from BN rats in which tumor had regressed were cultured in an in vitro mixed lymphocyte tumor cell culture (MLTC) to augment cytotoxicity of effector cells. In the MLTC a T cell subset was expanded in response to MST-1 antigens and transformed into blast elements. With these changes, there was an increase in the W3/25 antigen on the T cell surface, a decrease of W3/13 antigen, and an increase in the number of T cells with Ia antigens. The subset associated with elimination of established tumors was a blast T cell W3/25+, W3/13+, as detected by monoclonal antibodies to rat T antigens. The W3/25+ subset was poorly cytotoxic in vitro for MST-1 and apparently functioned in vivo as an amplifier or helper cell in the tumor-bearing host. The W3/25- population was a melange of cells that included (W3/13+, W3/25-) T cells, null cells, Ig+ cells, and macrophages, and was associated with enhancement of tumor in vivo, suggesting the presence of suppressor cells.
Assuntos
Antígenos de Histocompatibilidade Classe II/imunologia , Sarcoma Experimental/imunologia , Linfócitos T/imunologia , Animais , Antígenos de Superfície/imunologia , Feminino , Ratos , Receptores Imunológicos/imunologia , Baço/imunologia , Linfócitos T/transplante , Transplante IsogênicoRESUMO
Peritoneal macrophages endocytosed their histocompatibility antigens (RT1), Fc receptors (FcR), and concanavalin A (Con A) receptors after cross-linking by ligands, but did not cap these membrane proteins. The 323N cell, a "macrophage like" tumor cell, under identical conditions capped its surface proteins. Experiments measuring fluorescence recovery after photobleaching showed that the mobile fraction of RT1 was significantly greater in 323N cells than in normal peritoneal macrophages. Presumably, the membrane proteins of 323N are not as tethered to the cytoskeleton, or, if so, are in a nexus that is not the same as that which occurs between membrane proteins of normal macrophages and the cytoskeleton. The mobility of RT1 on normal lymphocytes was also different from that of macrophages. These observations suggest that the movement of membrane molecules is determined by cell type and is regulated by the cytoskeleton which varies in structure and function from cell type to cell type.
Assuntos
Transformação Celular Neoplásica , Macrófagos/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias Esplênicas/patologia , Animais , Colchicina/farmacologia , Antígenos de Histocompatibilidade , Linfócitos/metabolismo , Masculino , Ratos , Ratos Endogâmicos Lew , Receptores de Concanavalina A/metabolismo , Receptores Fc/metabolismoRESUMO
The Bio-Breeding/Worcester (BB/W) rat develops spontaneous autoimmune diabetes similar to human insulin-dependent diabetes mellitus. Transfusions of whole blood from the nondiabetic W-line of BB/W rats prevent the syndrome in diabetes-prone recipients. We report three experiments designed to determine which blood component is protective. In all experiments, diabetes-prone BB/W rats 23 to 35 d of age were given four or six weekly intravenous injections. In the first experiment, animals received either saline or transfusions of erythrocytes, white blood cells, or plasma from W-line donors. Diabetes occurred in 7/22 (32%) erythrocyte, 2/27 (7%) white cell, 14/24 (58%) plasma, and 15/27 (56%) saline recipients (P less than 0.001). At 120 d of age, peripheral blood was obtained from nondiabetic rats. Fluorescence-activated cell sorter analysis of OX 19 tagged leucocytes revealed 35% T lymphocytes in white cell recipients (n = 13), compared with 9% in saline recipients (n = 7; P less than 0.001). Responsiveness to concanavalin A was also increased in the white cell group, whereas the frequency of both insulitis and thyroiditis was decreased. In the second experiment, 1/19 (5%) rats transfused with W-line spleen cells developed diabetes, as contrasted with 12/18 (67%) recipients of diabetes-prone spleen cells and 19/31 (61%) noninjected controls (P less than 0.001). In the third experiment, diabetes-prone rats received either W-line blood treated with a cytotoxic anti-T lymphocyte antibody plus complement, untreated blood, or saline. Diabetes occurred in 8/20 (40%), 1/20 (5%), and 13/19 (68%) rats in each group, respectively (P less than 0.001). We conclude that transfusions of W-line T lymphocytes prevent diabetes in the BB/W rat.
Assuntos
Transfusão de Sangue , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Tipo 1/imunologia , Linfócitos T/transplante , Animais , Autoanticorpos/análise , Concanavalina A , Diabetes Mellitus Experimental/prevenção & controle , Diabetes Mellitus Tipo 1/prevenção & controle , Imunidade Inata , Ativação Linfocitária , Ratos , Ratos EndogâmicosRESUMO
To study mechanisms underlying resistance to cis-diamminedichloroplatinum (II) (cis-DDP) we have induced resistance to this agent in BE human colon carcinoma cells. A 5-fold increase in the IC50 of resistant compared to sensitive cells was noted as analyzed by the inhibition of cellular growth. Up to a 4-fold reduction in interstrand cross-link formation by cis-DDP in resistant compared to sensitive cells was present as measured by alkaline elution. No significant differences were detectable either in the extent of DNA platination as analyzed by atomic absorption spectroscopy or in the induction of cis-DDP DNA adducts as evaluated by an enzyme-linked immunosorbent assay employing antiserum that detects intrastrand cross-links formed by cis-DDP. Further, no differences in the kinetics of excision of DNA interstrand cross-links, cis-DDP DNA adducts, or total platinum in DNA were present. Levels of glutathione, however, were increased about threefold in resistant compared to sensitive cells. Loss of resistance was associated with increased interstrand cross-link formation and declines in glutathione levels. Our results are consistent with a critical role of glutathione in preventing platinum monoadduct rearrangements resulting in lower levels of interstrand cross-links and resistance to cis-DDP in resistant BE cells.
Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Células Tumorais Cultivadas/citologia , Ciclo Celular/efeitos dos fármacos , Neoplasias do Colo , Dano ao DNA , DNA de Neoplasias/análise , DNA de Neoplasias/efeitos dos fármacos , Resistência a Medicamentos , Ensaio de Imunoadsorção Enzimática , Glutationa/análise , Humanos , Cinética , Platina/análise , Compostos de Sulfidrila/análise , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
X-irradiation of purified primary cultures of mouse bone marrow stroma or permanent cloned marrow stromal cell lines in plateau phase decreases production of macrophage progenitor cell-specific colony-stimulating factor to a plateau minimum of 40% of control levels after doses of 50 to 500 Gy delivered at 2 Gy/min. After 50 Gy there is increased bioavailability of another growth factor(s) that is distinct from macrophage progenitor cell-specific colony-stimulating factor, granulocyte-macrophage progenitor cell colony-stimulating factor, or colony-stimulating factor for multipotential hematopoietic stem cells (interleukin 3). Liquid-phase cocultivation of irradiated stromal cells with either nonadherent cells from continuous marrow cultures or cloned dual granulocyte-macrophage progenitor cell colony-stimulating factor/interleukin 3-dependent hematopoietic progenitor cell lines induces evolution over 5 weeks of factor-independent colony-forming cells. Subcultured factor-independent colonies generated clonal malignant cell lines with multiple distinct karyotypic alterations. Inoculation of 10(6) cells s.c. from factor-independent clones into syngeneic mice produces local granulocytic monomyeloid tumors with spread to spleen, lymph nodes, and bone marrow. These data provide the first demonstration in vitro of indirect X-irradiation leukemogenesis through cells of the marrow stroma.
Assuntos
Medula Óssea/efeitos da radiação , Transformação Celular Neoplásica/efeitos da radiação , Células-Tronco Hematopoéticas/patologia , Leucemia Induzida por Radiação/etiologia , Animais , Células da Medula Óssea , Transformação Celular Neoplásica/patologia , Células Cultivadas , Fatores Estimuladores de Colônias/farmacologia , Substâncias de Crescimento/análise , Técnicas In Vitro , Interleucina-3 , Cariotipagem , Leucemia Induzida por Radiação/patologia , Linfocinas/farmacologia , Camundongos , Células-Tronco Neoplásicas/patologia , Raios XRESUMO
The response of BB diabetes-prone (DP) and W-line non-diabetes-prone rats to the T-cell mitogen concanavalin A (ConA) was measured. The W line was a good responder to ConA, whereas the DP was relatively unresponsive. This unresponsiveness could not be reversed with exogenous interleukin 2 (IL-2). The response of DP rats was enhanced by removing adherent cells. To directly test the response of BB T-cells, they were isolated by flow sorting. These experiments demonstrated that BB T-cells could mount a normal ConA response. The normal function of isolated BB T-cells suggested that they were under suppression. Suppressor activity could not be found in the OX8+ population but was found in the DP-adherent cell population. Adherent cells from the W line were not suppressive at the concentrations used. These results showed that the decreased mitogen responsiveness of BB T-cells was not due to an intrinsic T-cell abnormality but was due, in part, to suppression by adherent cells.
Assuntos
Concanavalina A/farmacologia , Ratos Endogâmicos BB/imunologia , Ratos Endogâmicos/imunologia , Linfócitos T/efeitos dos fármacos , Animais , Células Cultivadas , Diabetes Mellitus Experimental/imunologia , Interleucina-2/biossíntese , Ratos , Baço/citologia , Linfócitos T/metabolismo , Linfócitos T Reguladores/efeitos dos fármacosRESUMO
Diabetes-prone (DP) BB rats develop spontaneous autoimmune insulin-dependent diabetes mellitus (IDDM). The cell populations involved in the expression of diabetes are not precisely known but probably include natural killer (NK) cells, macrophages, and T lymphocytes. Because the DP rat has few lymphocytes of the CD5+/CD+ phenotype, cytotoxic T lymphocytes (Tc) are not believed to be important in the process. Diabetes-resistant (DR) BB rats that are depleted of RT6+ T lymphocytes also become diabetic and provide an additional model of IDDM. We report that diabetes in DR rats depleted of RT6+ T lymphocytes is prevented by the concomitant depletion of either the CD5+ or the CD8+ population. In contrast, coadministration of anti-asialogangliosideM1 (alpha-ASGM1), an antiserum that principally recognizes NK cells, failed to prevent hyperglycemia in RT6-depleted rats. We propose that the initiation of diabetes in both DP and RT6-depleted DR rats is T-lymphocyte dependent. However, the final common pathway leading to autoimmune beta-cell destruction in IDDM may be different in these models. The RT6-depleted DR rat requires a cell that is sensitive to anti-CD8 (possibly a Tc), whereas the DP rat requires an anti-ASGM1-sensitive cell.
Assuntos
ADP Ribose Transferases , Diabetes Mellitus Experimental/imunologia , Antígenos de Histocompatibilidade/imunologia , Glicoproteínas de Membrana , Linfócitos T/imunologia , Animais , Anticorpos Monoclonais/imunologia , Antígenos de Diferenciação/análise , Antígenos de Diferenciação de Linfócitos T/análise , Doenças Autoimunes/imunologia , Antígenos CD5 , Antígenos CD8 , Diabetes Mellitus Tipo 1/imunologia , Imunidade Inata , Ativação Linfocitária , Depleção Linfocítica , Fenótipo , Ratos , Ratos Endogâmicos BB , Baço/imunologiaRESUMO
Total lymphoid irradiation (TLI) at doses of 2200 rads or greater prevented diabetes in susceptible BB/W rats. Two of 29 (7%) treated rats became diabetic compared with 23 of 39 (59%) controls (P less than 0.001). TLI did not, however, prevent insulitis or thyroiditis in nondiabetic rats, nor did it restore the depressed concanavalin-A responsiveness of BB rat lymphocytes. T-lymphocyte subset proportions were the same in both groups. TLI was associated with significant radiation-related mortality, and nondiabetic TLI-treated rats weighed significantly less than controls. We conclude that TLI is effective in the prevention of BB rat diabetes. However, TLI fails to correct the subclinical immunologic abnormalities of the model and is associated with significant morbidity.
Assuntos
Diabetes Mellitus Tipo 1/prevenção & controle , Tecido Linfoide/efeitos da radiação , Animais , Doenças Autoimunes/prevenção & controle , Concanavalina A/farmacologia , Diabetes Mellitus Tipo 1/imunologia , Relação Dose-Resposta à Radiação , Feminino , Ilhotas Pancreáticas/imunologia , Masculino , Mitose/efeitos dos fármacos , Pancreatite/imunologia , Ratos , Linfócitos T/classificação , Tireoidite/imunologiaRESUMO
Autoimmune diabetes mellitus affects greater than 50% of diabetes-prone BB (DP BB) rats but less than 1% of diabetes-resistant BB (DR BB) rats. We report an outbreak of spontaneous diabetes among DR BB rats that coincided with serologic evidence of the onset of viral infection. This apparent link between a change in the environment and the expression of diabetes then led us to study the interaction of environmental exposure to viral pathogens in this disorder with virally seropositive and seronegative populations of BB rats and polyinosinic-polycytidylic acid (poly I:C), an interferon inducer known to accelerate diabetes onset in DP rats. We administered a cytotoxic anti-RT6 monoclonal antibody, poly I:C, or both to DR rats. Depletion of the RT6.1+T-lymphocyte population has previously been shown to induce diabetes and thyroiditis in DR rats. RT6 alone did not induce diabetes in seronegative DR rats, and poly I:C was only weakly effective, but nearly all animals given both reagents became diabetic. When given to seropositive DR rats, either reagent alone induced diabetes; when given to non-BB rats, neither agent was effective. Poly I:C also accelerated the onset of DP diabetes to a greater extent in seropositive than in seronegative rats. We conclude that expression of the genetic predisposition to diabetes present in all BB rats depends on cellular factors that include the presence or absence of regulatory (RT6+) T lymphocytes and modulatory environmental factors including exposure to viral pathogens.
Assuntos
ADP Ribose Transferases , Diabetes Mellitus Tipo 1/microbiologia , Glicoproteínas de Membrana , Ratos Endogâmicos BB/genética , Fenômenos Fisiológicos Virais , Animais , Anticorpos Monoclonais/toxicidade , Antígenos de Diferenciação de Linfócitos T , Causalidade , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patologia , Antígenos de Histocompatibilidade/imunologia , Interferons/metabolismo , Depleção Linfocítica , Poli I-C/farmacologia , Ratos , Linfócitos T/imunologia , Linfócitos T/patologia , Linfócitos T/fisiologia , Vírus/patogenicidadeRESUMO
BB rats develop spontaneous autoimmune insulin-dependent diabetes mellitus that is similar to human insulin-dependent diabetes. In this study, we used an in vitro islet cell cytotoxicity assay to study the possible role of natural killer (NK) cells and their soluble effector molecules in this disorder. First, the results demonstrated that in vivo treatment of acutely diabetic BB rats with anti-asialogangliosideM1 (an NK cell antiserum) but not with anti-T-lymphocyte antibodies reduces spleen cell cytotoxic activity to islets in vitro. Flow microfluorometry (FMF)-sorting experiments were then used to confirm that the splenic cytotoxic effector cell in acutely diabetic BB rats is a CD8+/CD5- NK cell. Further analysis demonstrated that both FMF-sorted NK cell populations from Wistar-Furth rats and unfractionated spleen cells from athymic nu/nu rats with high intrinsic NK cell activity also exhibit high islet cell cytotoxic activity in vitro. Finally, we found that the kinetics and differential cytotoxic activity of NK cells toward islets in vitro could be mimicked by NK cell culture supernatants containing high levels of NK cytotoxic factor (NKCF). The islet cytotoxic activity of these culture supernatants was specifically inhibited by the addition of anti-NKCF monoclonal antibody. These results demonstrate that NK cells from diabetic and nondiabetic rats are cytotoxic to islet cells in vitro. They further suggest that this cytotoxic effect may be mediated in part through the production and release of soluble factors such as NKCF.
Assuntos
Citotoxicidade Imunológica , Ilhotas Pancreáticas/imunologia , Células Matadoras Naturais/imunologia , Animais , Linhagem Celular , Células Cultivadas , Técnicas In Vitro , Depleção Linfocítica , Linfoma , Camundongos , Ratos , Ratos Endogâmicos , Ratos Endogâmicos WF , Especificidade da Espécie , Baço/imunologia , Linfócitos T/imunologiaRESUMO
A protocol consisting of a single donor-specific transfusion (DST) plus a brief course of anti-CD154 monoclonal antibody (anti-CD40 ligand mAb) induces permanent islet allograft survival in chemically diabetic mice, but its efficacy in mice with autoimmune diabetes is unknown. Confirming a previous report, we first observed that treatment of young female NOD mice with anti-CD154 mAb reduced the frequency of diabetes through 1 year of age to 43%, compared with 73% in untreated controls. We also confirmed that spontaneously diabetic NOD mice transplanted with syngeneic (NOD-Prkdc(scid)/Prkdc(scid)) or allogeneic (BALB/c) islets rapidly reject their grafts. Graft survival was not prolonged, however, by pretreatment with either anti-CD154 mAb alone or anti-CD154 mAb plus DST. In addition, allograft rejection in NOD mice was not restricted to islet grafts. Anti-CD154 mAb plus DST treatment failed to prolong skin allograft survival in nondiabetic male NOD mice. The inability to induce transplantation tolerance in NOD (H2g7) mice was associated with non-major histocompatibility complex (MHC) genes. Treatment with DST and anti-CD154 mAb prolonged skin allograft survival in both C57BL/6 (H2b) and C57BL/6.NOD-H2g7 mice, but it was ineffective in NOD, NOD.SWR-H2q, and NOR (H2g7) mice. Mitogen-stimulated interleukin-1beta production by antigen-presenting cells was greater in strains susceptible to tolerance induction than in the strains resistant to tolerance induction. The results suggest the existence of a general defect in tolerance mechanisms in NOD mice. This genetic defect involves defective antigen-presenting cell maturation, leads to spontaneous autoimmune diabetes in the presence of the H2g7 MHC, and precludes the induction of transplantation tolerance irrespective of MHC haplotype. Promising islet transplantation methods based on overcoming the alloimmune response by interference with costimulation may require modification or amplification for use in the setting of autoimmune diabetes.
Assuntos
Diabetes Mellitus Tipo 1/imunologia , Tolerância Imunológica , Transplante das Ilhotas Pancreáticas , Transplante de Pele , Animais , Anticorpos Monoclonais/uso terapêutico , Transfusão de Sangue , Ligante de CD40 , Feminino , Rejeição de Enxerto/prevenção & controle , Masculino , Glicoproteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Timectomia , Doadores de Tecidos , Condicionamento Pré-TransplanteRESUMO
Although acute interstitial nephritis has been documented during therapy with many antibiotics of the penicillin class, it has not previously been reported in association with carbenicillin therapy. We report here the case of a patient who developed the characteristic clinical features of this form of injury while receiving prolonged large doses of carbenicillin. Histologic examination confirmed the presence of a striking interstitial nephritis. Carbenicillin should be considered a potential cause of renal damage in patients who develop rash, eosinophilia, and microscopic hematuria in association with deterioration of renal function.
Assuntos
Carbenicilina/efeitos adversos , Nefrite Intersticial/induzido quimicamente , Doença Aguda , Idoso , Humanos , Rim/imunologia , Rim/patologia , Masculino , Nefrite Intersticial/imunologia , Nefrite Intersticial/patologiaRESUMO
Parvovirus B19 is a recently described pathogen, associated with an increasing spectrum of clinical manifestations. We present the first reported case, to our knowledge, of parvovirus B19-associated hemophagocytic syndrome, in which the diagnosis of parvovirus infection was documented by the presence of B19-specific IgM and IgG antibodies. Pancytopenia resolved immediately following splenectomy and the patient recovered completely.
Assuntos
Histiocitose de Células não Langerhans/diagnóstico , Infecções por Parvoviridae/diagnóstico , Anticorpos Antivirais/análise , Criança , Histiocitose de Células não Langerhans/etiologia , Humanos , Masculino , Parvoviridae/isolamento & purificação , Infecções por Parvoviridae/patologia , Baço/patologiaRESUMO
Four patients fulfilling the case definition for eosinophilia-myalgia syndrome are described, including one whose disease began in 1986. Each displayed a variety of symptoms: one suffered principally from myalgia and recovered spontaneously on discontinuation of L-tryptophan therapy; one exhibited progressive sclerodermiform skin changes, neuropathy, and myopathy; a third had prominent neuromuscular disease and sclerodermiform skin changes; and the fourth experienced profound weight loss, an axonal polyneuropathy, and perivascular lymphoid infiltrates simulating a lymphoma. Evidence of T-cell activation was present in peripheral blood and affected tissues during the clinically active progressive phase of disease. Among other manifestations pleural effusion, cutaneous vasculitis, joint contractures, and bloody diarrhea were observed. A history of L-tryptophan ingestion should be sought in patients with myalgia, fatigue, or the above outlined symptoms.
Assuntos
Eosinofilia/induzido quimicamente , Doenças Musculares/induzido quimicamente , Triptofano/efeitos adversos , Adulto , Idoso , Eosinofilia/diagnóstico , Eosinofilia/epidemiologia , Feminino , Humanos , Masculino , Massachusetts/epidemiologia , Músculos/patologia , Doenças Musculares/diagnóstico , Doenças Musculares/epidemiologia , Automedicação , Pele/patologia , SíndromeRESUMO
Combined retroperitoneal and mediastinal fibrosis is a rare manifestation of an idiopathic systemic sclerosing disease. This report describes a multisystem illness that clinically could best be described as polyserositis and progressive renal failure. Pathologically, it was characterized by diffuse infiltration of retroperitoneal and mediastinal tissues with plaquelike fibrofatty connective tissue encasing the kidneys, ureters, adrenal glands, and parietal pericardium. These features are diagnostic of a systemic sclerosing disease. It is important to recognize this unusual disorder to avoid confusion with other systemic connective tissue diseases such as systemic lupus erythematosus.
Assuntos
Doenças do Tecido Conjuntivo/diagnóstico , Mediastino/patologia , Fibrose Retroperitoneal/diagnóstico , Idoso , Diagnóstico Diferencial , Feminino , Fibrose , Humanos , Fibrose Retroperitoneal/patologiaRESUMO
The ability to diagnose prostate carcinoma would be improved by the detection of a tumor-associated antigen. P504S, a cytoplasmic protein, was recently identified by cDNA library subtraction in conjunction with high throughput microarray screening from prostate carcinoma. The aim of this study was to establish the pattern of expression of P504S in prostate carcinoma and benign prostatic tissue. A total of 207 cases, including 137 cases of prostate carcinoma and 70 cases of benign prostate, from prostatectomies (n = 77), prostate needle biopsies (n = 112), and transurethral prostate resections (n = 18) were examined by immunocytochemistry for P504S. P504S showed strong cytoplasmic granular staining in 100% of prostate carcinomas regardless of Gleason scores and diffuse (>75% of tumor) staining in 92% of cases. In contrast, 171 of 194 (88%) of benign prostates, including 56 of 67 (84%) benign prostate cases and 115 of 127 (91%) cases of benign glands adjacent to cancers were negative for P504S. The remainders of benign prostates were focally and weakly positive for P504S. The staining pattern of these normal glands was different and easily distinguishable from that observed in prostate carcinoma. Expression of P504S was not found in basal cell hyperplasia, urothelial cells/metaplasia and small atrophic glands that may mimic prostate carcinoma. Our findings indicate that P504S is a highly sensitive and specific positive marker for prostate carcinoma.
Assuntos
Biomarcadores Tumorais , Carcinoma/diagnóstico , Neoplasias da Próstata/diagnóstico , Racemases e Epimerases , Anticorpos Monoclonais , Western Blotting , Carcinoma/enzimologia , Carcinoma/cirurgia , Humanos , Técnicas Imunoenzimáticas , Queratinas/metabolismo , Masculino , Peso Molecular , Próstata/enzimologia , Próstata/patologia , Próstata/cirurgia , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/cirurgia , Racemases e Epimerases/metabolismoRESUMO
BACKGROUND: Treatment with a donor-specific transfusion (DST) and a brief course of anti-mouse CD154 (anti-CD40-ligand) monoclonal antibody (mAb) prolongs the survival of both allografts and rat xenografts in mice. The mechanism by which allograft survival is prolonged is incompletely understood, but depends in part on the presence of CD4+ cells and the deletion of alloreactive CD8+ T cells. Less is known about the mechanism by which this protocol prolongs xenograft survival. METHODS: We measured rat islet and skin xenograft survival in euthymic and thymectomized mice treated with combinations of DST, anti-CD154 mAb, anti-CD4 mAb, and anti-CD8 mAb. Recipients included C57BL/6, C57BL/6-scid, C57BL/6-CD4null, and C57BL/6-CD8null mice. RESULTS: Pretreatment with a depleting anti-CD4 mAb markedly prolonged the survival of both skin and islet xenografts in mice given DST plus anti-CD154 mAb. Comparable prolongation of xenograft survival was obtained in C57BL/6-CD4null recipients treated with DST and anti-CD154 mAb. In contrast, anti-CD8 mAb did not prolong the survival of either islet or skin xenografts in mice treated with DST and anti-CD154 mAb. Thymectomy did not influence xenograft survival in any treatment group. Adoptive transfer of splenocytes from C57BL/6-CD4null recipients treated with DST and anti-CD154 mAb and bearing long-term skin xenografts revealed the presence of residual xenoreactive cells. CONCLUSIONS: These data suggest that treatment with DST and anti-CD154 mAb induces a state of "functional" transplantation tolerance. They also support the hypothesis that both the induction and maintenance of graft survival based on this protocol depend on different cellular mechanisms in allogeneic and xenogeneic model systems.
Assuntos
Transfusão de Sangue , Linfócitos T CD4-Positivos/citologia , Ligante de CD40/imunologia , Sobrevivência de Enxerto/fisiologia , Transplante Heterólogo/imunologia , Animais , Anticorpos/uso terapêutico , Sobrevivência de Enxerto/imunologia , Depleção Linfocítica , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Endogâmicos LewRESUMO
BACKGROUND: Posttransplant lymphoproliferative disorders are generally associated with Epstein-Barr virus (EBV) and are of B cell origin. We report the case of a B-immunoblastic lymphoma that developed in a pretransplantation EBV-seronegative woman 4 months after kidney transplant from her HLA-haploidentical brother. The patient successfully underwent immunotoxin therapy for lymphoma and has been in remission for 36 months. METHODS: Latent EBV genomes were identified by polymerase chain reaction, and the purified amplification products were directly sequenced with [35S]dATP. RESULTS: Molecular analysis of the latent membrane protein (LMP)1 oncogene of EBV, which was expressed in most tumor cells, revealed a 30-base pair deletion. No wild-type LMP1 sequences were found. Analysis of peripheral blood mononuclear cells from the EBV-seropositive donor showed the presence of both the LMP1 deletion variant and the wild-type sequence. The LMP1 deletion variant and the wild-type sequence were also identified within peripheral blood mononuclear cells of the EBV-seroconverted kidney recipient 20 months after lymphoma therapy. CONCLUSION: This pattern is consistent with a natural growth advantage of B cells expressing the LMP1 deletion variant in the immunocompromised host.